Thomas Gajewski

Summary

Affiliation: University of Chicago
Country: USA

Publications

  1. pmc Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells
    Mercedes B Fuertes
    Department of Pathology and Department of Medicine, Section of Hematology Oncology, The University of Chicago, Chicago, IL, USA
    J Exp Med 208:2005-16. 2011
  2. pmc Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivo
    Yan Zheng
    Department of Pathology and 2 Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 209:2157-63. 2012
  3. pmc Evidence implicating the Ras pathway in multiple CD28 costimulatory functions in CD4+ T cells
    Sujit V Janardhan
    Department of Pathology, The University of Chicago, Chicago, Illinois, United States of America
    PLoS ONE 6:e24931. 2011
  4. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma Bridge. Napoli, December 2nd-4th 2012"
    Paolo A Ascierto
    Istituto Nazionale Tumori, Fondazione G, Pascale, Naples, Italy
    J Transl Med 11:137. 2013
  5. pmc Cancer classification using the Immunoscore: a worldwide task force
    Jerome Galon
    INSERM, U872, Laboratory of Integrative Cancer Immunology, Paris, F 75006, France
    J Transl Med 10:205. 2012
  6. pmc Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011
    Ivan Martinez Forero
    Centro de Investigación Médica Aplicada, Universidad de Navarra, Avda Pio XII, 55, 31008 Pamplona, Spain
    J Transl Med 10:108. 2012
  7. ncbi request reprint Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment
    Thomas F Gajewski
    University of Chicago, United States
    Curr Opin Immunol 25:268-76. 2013
  8. pmc Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104)
    Thomas F Gajewski
    The University of Chicago, Section of Hematology Oncology, 5841 S, Maryland Ave, MC2115, Chicago, IL 60637, USA
    J Transl Med 10:246. 2012
  9. doi request reprint Innate immune sensing of cancer: clues from an identified role for type I IFNs
    Thomas F Gajewski
    Department of Pathology, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637, USA
    Cancer Immunol Immunother 61:1343-7. 2012
  10. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma research: a bridge from Naples to the World. Napoli, December 5th-6th 2011"
    Paolo A Ascierto
    Department of Melanoma, Sarcoma, and Head and Neck Disease, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
    J Transl Med 10:83. 2012

Research Grants

  1. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas Gajewski; Fiscal Year: 2007
  2. Countering immune resistance in the melanoma tumor microenvironment
    Thomas F Gajewski; Fiscal Year: 2010
  3. Multi-Peptide/IL 12 Melanoma Vaccine
    Thomas Gajewski; Fiscal Year: 2003
  4. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2004
  5. DGK in T Cell Regulation and Tolerance
    Thomas Gajewski; Fiscal Year: 2009
  6. Multi-Peptide/IL 12 Melanoma Vaccine
    Thomas Gajewski; Fiscal Year: 2006
  7. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas F Gajewski; Fiscal Year: 2010
  8. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2005
  9. Technologies To Block Gene Expression in Normal T Cells
    Thomas Gajewski; Fiscal Year: 2003
  10. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2003

Detail Information

Publications93

  1. pmc Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells
    Mercedes B Fuertes
    Department of Pathology and Department of Medicine, Section of Hematology Oncology, The University of Chicago, Chicago, IL, USA
    J Exp Med 208:2005-16. 2011
    ..Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α(+) DCs...
  2. pmc Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivo
    Yan Zheng
    Department of Pathology and 2 Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 209:2157-63. 2012
    ..Using superantigen- and tumor-induced anergy models, we found that Egr2 is necessary for anergy induction in vivo. Collectively, our results implicate Egr2 as an essential transcriptional regulator of the T cell anergy program...
  3. pmc Evidence implicating the Ras pathway in multiple CD28 costimulatory functions in CD4+ T cells
    Sujit V Janardhan
    Department of Pathology, The University of Chicago, Chicago, Illinois, United States of America
    PLoS ONE 6:e24931. 2011
    ..Finally, active Ras was able to induce IL-2 production when combined with ionomycin stimulation in a MEK-1-dependent fashion. Our results are consistent with a central role for Ras signaling in CD28-mediated costimulation...
  4. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma Bridge. Napoli, December 2nd-4th 2012"
    Paolo A Ascierto
    Istituto Nazionale Tumori, Fondazione G, Pascale, Naples, Italy
    J Transl Med 11:137. 2013
    ....
  5. pmc Cancer classification using the Immunoscore: a worldwide task force
    Jerome Galon
    INSERM, U872, Laboratory of Integrative Cancer Immunology, Paris, F 75006, France
    J Transl Med 10:205. 2012
    ..The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune)...
  6. pmc Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011
    Ivan Martinez Forero
    Centro de Investigación Médica Aplicada, Universidad de Navarra, Avda Pio XII, 55, 31008 Pamplona, Spain
    J Transl Med 10:108. 2012
    ..The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace...
  7. ncbi request reprint Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment
    Thomas F Gajewski
    University of Chicago, United States
    Curr Opin Immunol 25:268-76. 2013
    ..New therapeutic interventions are being guided by these observations, and preliminary clinical success is validating this working model...
  8. pmc Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104)
    Thomas F Gajewski
    The University of Chicago, Section of Hematology Oncology, 5841 S, Maryland Ave, MC2115, Chicago, IL 60637, USA
    J Transl Med 10:246. 2012
    ..As farnesylated proteins are also important for T cell activation, measurement of effects on T cell function was also pursued...
  9. doi request reprint Innate immune sensing of cancer: clues from an identified role for type I IFNs
    Thomas F Gajewski
    Department of Pathology, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637, USA
    Cancer Immunol Immunother 61:1343-7. 2012
    ..Elucidating further these innate immune mechanisms should provide new insights into cancer immunotherapy...
  10. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma research: a bridge from Naples to the World. Napoli, December 5th-6th 2011"
    Paolo A Ascierto
    Department of Melanoma, Sarcoma, and Head and Neck Disease, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
    J Transl Med 10:83. 2012
    ....
  11. pmc Defining the critical hurdles in cancer immunotherapy
    Bernard A Fox
    Earle A, Chiles Research Institute, Robert W, Franz Research Center, Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA
    J Transl Med 9:214. 2011
    ..Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer...
  12. pmc The immune score as a new possible approach for the classification of cancer
    Jerome Galon
    INSERM, U872, Laboratory of Integrative Cancer Immunology, 15 Rue de l Ecole de Medecine F 75006 Paris, France
    J Transl Med 10:1. 2012
    ....
  13. pmc SITC/iSBTc Cancer Immunotherapy Biomarkers Resource Document: online resources and useful tools - a compass in the land of biomarker discovery
    Davide Bedognetti
    Society for Immunotherapy of Cancer, Milwaukee, WI, USA
    J Transl Med 9:155. 2011
    ..This organized collection of the most useful references, online resources and tools serves as a compass to guide discovery of biomarkers essential to advancing novel cancer immunotherapies...
  14. pmc Review of the 25th annual scientific meeting of the International Society for Biological Therapy of Cancer
    James M Balwit
    Society for Immunotherapy of Cancer, Milwaukee, WI, USA
    J Transl Med 9:60. 2011
    ....
  15. ncbi request reprint Absence of CTLA-4 lowers the activation threshold of primed CD8+ TCR-transgenic T cells: lack of correlation with Src homology domain 2-containing protein tyrosine phosphatase
    T F Gajewski
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 166:3900-7. 2001
    ..Thus, the biochemical mechanism explaining the differential inhibitory effect of CTLA-4 on naive and primed CD8(+) T cells remains unclear...
  16. ncbi request reprint Immune suppression in the tumor microenvironment
    Thomas F Gajewski
    Department of Pathology and Department of Medicine University of Chicago, Chicago, IL 60637, USA
    J Immunother 29:233-40. 2006
    ....
  17. ncbi request reprint Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment
    Thomas F Gajewski
    Departments of Pathology and Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Clin Cancer Res 13:5256-61. 2007
    ..Recognition of these evasion mechanisms has pointed toward new therapeutic approaches for cancer immunotherapy...
  18. ncbi request reprint Identifying and overcoming immune resistance mechanisms in the melanoma tumor microenvironment
    Thomas F Gajewski
    Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    Clin Cancer Res 12:2326s-2330s. 2006
    ..Importantly, each of these targets is amenable to clinical manipulation. Clinical translation of these approaches to counter negative regulation of antitumor immunity should receive high priority...
  19. pmc Molecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment
    Thomas F Gajewski
    The University of Chicago, Chicago, IL 60636, USA
    Curr Opin Immunol 23:286-92. 2011
    ..But in addition, characterization of these subsets may pave the way for catering therapeutic interventions toward the biologic features of the tumor in individual patients...
  20. doi request reprint Gene signature in melanoma associated with clinical activity: a potential clue to unlock cancer immunotherapy
    Thomas F Gajewski
    University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA
    Cancer J 16:399-403. 2010
    ....
  21. ncbi request reprint Overcoming immune resistance in the tumor microenvironment by blockade of indoleamine 2,3-dioxygenase and programmed death ligand 1
    Thomas F Gajewski
    Department of Pathology, Section of Hematology Oncology, The University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA
    Curr Opin Investig Drugs 5:1279-83. 2004
    ..Blockade of these molecules may increase the efficacy of tumor-specific T-cell therapies in cancer patients...
  22. ncbi request reprint The expanding universe of regulatory T cell subsets in cancer
    Thomas F Gajewski
    University of Chicago, Chicago, IL 60637, USA
    Immunity 27:185-7. 2007
    ..In this issue of Immunity, Peng et al. (2007) add to this list by describing tumor-infiltrating gammadelta T cells that have regulatory function...
  23. ncbi request reprint Immune resistance orchestrated by the tumor microenvironment
    Thomas F Gajewski
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    Immunol Rev 213:131-45. 2006
    ..Identification of these downstream processes points to new therapeutic targets that should be manipulated to facilitate the effector phase of anti-tumor immune responses in concert with vaccination or T-cell adoptive transfer...
  24. ncbi request reprint Phase II trial of the O6-alkylguanine DNA alkyltransferase inhibitor O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea in advanced melanoma
    Thomas F Gajewski
    Department of Medicine, University of Chicago, IL 60637, USA
    Clin Cancer Res 11:7861-5. 2005
    ..We postulated that the addition of O(6) benzylguanine (O(6)BG), a potent inactivator of AGT, would improve the clinical response to BCNU in melanoma...
  25. pmc Molecular profiling of melanoma and the evolution of patient-specific therapy
    Thomas F Gajewski
    Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
    Semin Oncol 38:236-42. 2011
    ....
  26. ncbi request reprint Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines
    Katharina Tschoep
    Department of Pathology, Section of Hematology Oncology, University of Chicago, Illinois, USA
    J Leukoc Biol 74:69-80. 2003
    ..Our results suggest that the functions thought to contribute to optimal T cell priming are not coexpressed by the same DC population and that immature and mature DC likely possess distinct CD40-mediated signaling events...
  27. ncbi request reprint Integrating IL-12 into therapeutic cancer vaccines
    Thomas F Gajewski
    Departments of Pathology and Medicine, Section of Hematology Oncology, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA
    Cancer Chemother Biol Response Modif 20:343-9. 2002
  28. ncbi request reprint Immunization of HLA-A2+ melanoma patients with MAGE-3 or MelanA peptide-pulsed autologous peripheral blood mononuclear cells plus recombinant human interleukin 12
    T F Gajewski
    Department of Pathology, The University of Chicago, Illinois 60637, USA
    Clin Cancer Res 7:895s-901s. 2001
    ..Outgrowth of antigen-negative tumors argues for the future development of polyepitope vaccines...
  29. ncbi request reprint Cutting edge: spontaneous rejection of poorly immunogenic P1.HTR tumors by Stat6-deficient mice
    A K Kacha
    Department of Pathology and the Committee on Immunology, Section of Hematology Oncology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 165:6024-8. 2000
    ..Rejection was accompanied by augmented tumor-specific IFN-gamma production and CTL activity. These results suggest that pharmacologic inhibition of Stat6 signaling could potentiate anti-tumor immunity in vivo...
  30. ncbi request reprint Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A
    M A Markiewicz
    Department of Pathology, University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA
    Int Immunol 13:625-32. 2001
    ..A broadened CTL response may help eliminate outgrowth of antigen-negative tumor variants...
  31. ncbi request reprint CD28 is not required for c-Jun N-terminal kinase activation in T cells
    F V Rivas
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 167:3123-8. 2001
    ..Thus, CD28 coligation is not necessary, and stimulation through the TCR is sufficient, for JNK activation in normal murine T cells. The concept that JNK mediates the costimulatory function of CD28 needs to be reconsidered...
  32. ncbi request reprint B7.1 is a quantitatively stronger costimulus than B7.2 in the activation of naive CD8+ TCR-transgenic T cells
    P E Fields
    Department of Pathology, University of Chicago, IL 60637, USA
    J Immunol 161:5268-75. 1998
    ..2. Further, our results indicate that the activation state of the responding T cell may influence the efficiency with which the T cell can respond to a costimulatory signal provided by either B7.1 or B7.2...
  33. pmc B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28
    F Fallarino
    Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 188:205-10. 1998
    ..Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4...
  34. ncbi request reprint Cutting edge: differentiation of antitumor CTL in vivo requires host expression of Stat1
    F Fallarino
    Department of Pathology, Department of Medicine, Section of Hematology Oncology, University of Chicago, IL 60637, USA
    J Immunol 163:4109-13. 1999
    ..Lack of cytolytic function correlated with a failure to up-regulate serine esterase activity. Thus, IFN-mediated signaling on host cells is required for the development of antitumor lytic effector cells...
  35. doi request reprint Phase II study of immunomodulation with granulocyte-macrophage colony-stimulating factor, interleukin-2, and rituximab following autologous stem cell transplant in patients with relapsed or refractory lymphomas
    Xavier Poiré
    Department of Medicine, University of Chicago Medical Center, Chicago, IL 60637, USA
    Leuk Lymphoma 51:1241-50. 2010
    ..Post-ASCT immunomodulation with rituximab, IL-2, and GM-CSF was feasible and safe, but not all patients were able to continue on to post-ASCT immunotherapy...
  36. ncbi request reprint Expression and function of CTLA-4 in Th1 and Th2 cells
    M L Alegre
    Howard Hughes Medical Institute, University of Chicago, IL 60637, USA
    J Immunol 161:3347-56. 1998
    ..We conclude that CTLA-4 can function to suppress the production of cytokines produced by both Th1 and Th2 cells...
  37. ncbi request reprint Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience
    A S Artz
    University of Chicago Hospitals, Chicago, IL 60637 1470, USA
    Bone Marrow Transplant 35:253-60. 2005
    ..002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification...
  38. ncbi request reprint Clinical responses following nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma are associated with expansion of CD8+ IFN-gamma-producing T cells
    H Harlin
    Department of Pathology, The University of Chicago, IL 60637, USA
    Bone Marrow Transplant 33:491-7. 2004
    ..Our results support the hypothesis that the antitumor effects of NST may be mediated by IFN-gamma-producing CD8+ T cells, and indicate that isolation of putative tumor antigen-specific T cells, ideally, should be pursued around day +180...
  39. ncbi request reprint Antigen-specific blockade of T cells in vivo using dimeric MHC peptide
    S M O'Herrin
    The Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 167:2555-60. 2001
    ..The prolonged Ag-specific suppression of expansion and/or effector function of cognate T cells in vivo suggests that soluble MHC dimers may be a means of inducing sustained Ag-specific T cell unresponsiveness in vivo...
  40. doi request reprint The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma
    Howard L Kaufman
    Rush University Cancer Center, 1725 West Harrison Street, Chicago, IL 60612, USA
    Nat Rev Clin Oncol 10:588-98. 2013
    ..Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted...
  41. ncbi request reprint Depletion of normal B cells with rituximab as an adjunct to IL-2 therapy for renal cell carcinoma and melanoma
    M Aklilu
    Department of Medicine, Section of Hematology Oncology, University of Chicago, Chicago, IL, USA
    Ann Oncol 15:1109-14. 2004
    ..We postulated that in patients with metastatic renal cell carcinoma (RCC) or melanoma, depletion of normal B cells using the anti-CD20 mAb rituximab before treatment with low-dose interleukin (IL)-2 would improve clinical outcome...
  42. ncbi request reprint Phenotypic and functional analysis of murine CD3+,CD4-,CD8- TCR-gamma delta-expressing peripheral T cells
    R Q Cron
    University of Chicago, Ben May Institute, Department of Pathology, IL 60637
    J Immunol 142:3754-62. 1989
    ..Finally, activated CD3+, CD4-,CD8-,TCR-gamma delta+ splenocytes were also capable of producing IL-2, IL-3, IFN-gamma, and TNF when stimulated in vitro with anti-CD3-epsilon mAb...
  43. pmc CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells
    Luciana L Molinero
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    J Immunol 182:6736-43. 2009
    ..These data suggest a modified model of nTreg development in which TCR-CBM-dependent signals are essential to commit immature thymocytes to the nTreg lineage...
  44. ncbi request reprint Peripheral survival of naïve CD8+ T cells
    I E Brown
    Department of Pathology, University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637, USA
    Apoptosis 10:5-11. 2005
    ..We also discuss associations between survival and homeostasis-driven proliferation, and highlight the gaps in our knowledge of these critical processes...
  45. ncbi request reprint The p815 mastocytoma tumor model
    T F Gajewski
    The University of Chicago, Chicago, Illinois, USA
    Curr Protoc Immunol . 2001
    ....
  46. ncbi request reprint Homeostatic proliferation as an isolated variable reverses CD8+ T cell anergy and promotes tumor rejection
    Ian E Brown
    Department of Pathology and Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    J Immunol 177:4521-9. 2006
    ..Taken together, our data suggest that a major mechanism by which homeostatic proliferation supports tumor rejection is by maintaining and/or re-establishing T cell responsiveness...
  47. pmc Farnesyltransferase inhibitors inhibit T-cell cytokine production at the posttranscriptional level
    Reinhard E Marks
    Department of Pathology, University of Chicago, IL, USA
    Blood 110:1982-8. 2007
    ..These results indicate that FTIs inhibit T-cell activation at the posttranscriptional level and also suggest that they may have potential as novel immunosuppressive agents...
  48. pmc Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases
    Ping Yu
    Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 179:1960-8. 2007
    ..Therefore, targeting the primary tumor with Ad-LIGHT before surgical excision is a new strategy to elicit better immune response for the eradication of spontaneous metastases...
  49. pmc An adenoviral vector encoding dominant negative Cbl lowers the threshold for T cell activation in post-thymic T cells
    Yuanyuan Zha
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    Cell Immunol 247:95-102. 2007
    ..Our results indicate that introduction of dominant negative Cbl can potentiate activation of post-thymic CD4+ T cells, which argues for development of strategies to interfere with Cbl function as a method of immunopotentiation...
  50. pmc Use of Cre-adenovirus and CAR transgenic mice for efficient deletion of genes in post-thymic T cells
    Yuanyuan Zha
    Department of Pathology and Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    J Immunol Methods 331:94-102. 2008
    ..This technology should be broadly applicable for studies of T cell-specific gene deletion to gain understanding of function in the post-thymic T cell compartment...
  51. doi request reprint Production of TH1 and TH2 cell lines and clones
    FRANK W FITCH
    University of Chicago, Chicago, Illinois, USA
    Curr Protoc Immunol . 2006
    ..Support protocols describe a micromanipulation method for cloning T cells and a roadmap for using protocols published elsewhere in this series to assess cytokine production by T cell clones and lines...
  52. doi request reprint Homeostatic proliferation plus regulatory T-cell depletion promotes potent rejection of B16 melanoma
    Justin Kline
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Clin Cancer Res 14:3156-67. 2008
    ..To investigate the antitumor efficacy of T-cell anergy reversal through homeostatic proliferation and regulatory T-cell (Treg) depletion in a clinically relevant murine adoptive immunotherapy model...
  53. pmc Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells
    Candace M Cham
    Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA
    Eur J Immunol 38:2438-50. 2008
    ....
  54. ncbi request reprint Death of peripheral CD8+ T cells in the absence of MHC class I is Fas-dependent and not blocked by Bcl-xL
    Mary A Markiewicz
    Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
    Eur J Immunol 33:2917-26. 2003
    ..These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8(+) T cells die via a Fas-dependent, mitochondria-independent pathway...
  55. ncbi request reprint Report on the ISBTC mini-symposium on biologic effects of targeted therapeutics
    Michael B Atkins
    Beth Israel Deaconess Medical Center, Boston, MA, USA
    J Immunother 30:577-90. 2007
    ....
  56. ncbi request reprint Induction of cytotoxic granules in human memory CD8+ T cell subsets requires cell cycle progression
    Yuru Meng
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 177:1981-7. 2006
    ..The fact that granule induction can be achieved through TCR and CD28 ligation has implications for restoring lytic effector function in the context of antitumor immunity...
  57. ncbi request reprint Negative regulation of T-cell function by PD-1
    Yuan Yuan Zha
    University of Chicago, Department of Pathology, Section of Hematology Oncology, Chicago, IL 60637, USA
    Crit Rev Immunol 24:229-37. 2004
    ..This review summarizes data regarding PD-1 and related negative regulatory receptors, focusing on implications for potentiating antitumor immunity in vivo...
  58. ncbi request reprint Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignancies
    Todd M Zimmerman
    Department of Medicine, Section of Hematology Oncology, University of Chicago, Chicago, IL, USA
    J Clin Oncol 22:4816-22. 2004
    ..Tipifarnib, an orally bioavailable inhibitor of farnesyl transferase, has activity in hematologic malignancies, but the dose required to achieve the proposed biologic end point, inhibition of farnesylation, is unknown...
  59. pmc Formation of a central supramolecular activation cluster is not required for activation of naive CD8+ T cells
    James P O'Keefe
    Committee on Cancer Biology and Department of Pathology, University of Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 101:9351-6. 2004
    ....
  60. ncbi request reprint PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells
    Christian Blank
    Department of Pathology, Section of Hematology Oncology, The University of Chicago, Chicago, Illinois, USA
    Cancer Res 64:1140-5. 2004
    ..Our results support interfering with PD-L1/PD-1 interactions to augment the effector function of tumor antigen-specific CD8(+) T cells in the tumor microenvironment...
  61. pmc Actin cytoskeleton regulates calcium dynamics and NFAT nuclear duration
    Fabiola V Rivas
    Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell Biol 24:1628-39. 2004
    ..Our results imply a novel role for the actin cytoskeleton in modulating the duration of Ca(2+)-NFAT signaling and indicate that actin dynamics regulate features of T-cell activation downstream of receptor clustering...
  62. ncbi request reprint Temozolomide for melanoma: new toxicities and new opportunities
    Thomas F Gajewski
    J Clin Oncol 22:580-1. 2004
  63. ncbi request reprint Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells
    Christian Blank
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 171:4574-81. 2003
    ..Our results are consistent with a model in which absence of PD-1 leads to greater negative selection of strongly interacting DP cells as well as increased emergence of DN alphabeta peripheral T cells...
  64. ncbi request reprint T cell development and function in CrkL-deficient mice
    Amy C Peterson
    Department of Medicine, Section of Hematology Oncology, University of Chicago, Chicago, IL 60637, USA
    Eur J Immunol 33:2687-95. 2003
    ..Our results indicate that CrkL is not absolutely required for T cell development or function, and argue against it being an essential component of a negative regulatory pathway in TCR signaling...
  65. pmc B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism
    Xingluo Liu
    Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA
    J Exp Med 197:1721-30. 2003
    ..Our results demonstrate a novel pathway for B7DC to promote tumor immunity and may reconcile the apparently contradictory findings on the function of B7DC...
  66. ncbi request reprint Immunization with Melan-A peptide-pulsed peripheral blood mononuclear cells plus recombinant human interleukin-12 induces clinical activity and T-cell responses in advanced melanoma
    Amy C Peterson
    Department of Pathology, University of Chicago, IL 60637, USA
    J Clin Oncol 21:2342-8. 2003
    ..A phase II study of immunization with Melan-A peptide-pulsed PBMC + rhIL-12 was conducted in 20 patients with advanced melanoma...
  67. ncbi request reprint A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer
    Jerome D Winegarden
    The Department of Medicine, Section of Hematology and Oncology, University of Chicago Medical Center, University of Chicago Cancer Center and the Phase II Network, 5841 S Maryland Avenue MC2115, Chicago, IL 60637, USA
    Lung Cancer 39:191-6. 2003
    ..Bryostatin-1 is a macrocyclic lactone, which exhibits pleiotropic biological effects via protein kinase C and has shown preclinical synergy with paclitaxel for enhanced tumor cell apoptosis...
  68. ncbi request reprint Increasing tumor antigen expression overcomes "ignorance" to solid tumors via crosspresentation by bone marrow-derived stromal cells
    Michael T Spiotto
    Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
    Immunity 17:737-47. 2002
    ..Thus, tumor antigens expressed at levels sufficient for crosspresentation by bone marrow-derived stromal cells may overcome immunological "ignorance" to solid tumors...
  69. ncbi request reprint Cutting edge: targeted ligation of CTLA-4 in vivo by membrane-bound anti-CTLA-4 antibody prevents rejection of allogeneic cells
    Kwang Woo Hwang
    Department of Medicine and Committee in Immunology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 169:633-7. 2002
    ..Furthermore, CTLA-4(+/+) T cells that had encountered 7M-expressing tumors in vivo acquired defects in cytokine production and cytotoxicity. Thus, deliberate ligation of CTLA-4 in vivo potently inhibits allogeneic T cell responses...
  70. ncbi request reprint Flt-3 ligand and sequential FL/interleukin-2 in patients with metastatic renal carcinoma: clinical and biologic activity
    Brian I Rini
    Department of Medicine, Section of Hematology Oncology, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, U S A
    J Immunother 25:269-77. 2002
    ....
  71. ncbi request reprint Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy
    Christian Blank
    Department of Hematology and Oncology, University of Regensburg, Franz Josef Strauss Allee 11, 93042 Regensburg, Germany
    Cancer Immunol Immunother 54:307-14. 2005
    ..This review discusses the currently available data concerning negative T-cell regulation via PD-1, the blockade of PD-L1/PD-1 interactions, and the implications for adoptive T-cell therapies...
  72. ncbi request reprint Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 in advanced melanoma: Cancer and Leukemia Group B 509901
    John D Roberts
    Virginia Commonwealth University, Richmond, Virgina 23298 0037, USA
    J Immunother 29:95-101. 2006
    ..The combination of g209-2M and low-dose IL-2 is safe and tolerable but inactive against advanced melanoma. Absence of evidence of immunization raises concerns for peptide-based immunization strategies with concurrent IL-2...
  73. ncbi request reprint Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro
    Christian Blank
    Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany
    Int J Cancer 119:317-27. 2006
    ..In summary, our data suggest that PD-L1/PD-1 interactions negatively regulate T cell effector functions predominantly in the absence of exogenous cytokine support, indicating an important role for this pathway in tumor evasion...
  74. ncbi request reprint Cross-priming of T cells to intracranial tumor antigens elicits an immune response that fails in the effector phase but can be augmented with local immunotherapy
    Simona Velicu
    Division of Neurosurgery, The University of Chicago, Pritzker School of Medicine, 5841 S Maryland Ave MC 3026, Chicago, IL 60637, USA
    J Neuroimmunol 174:74-81. 2006
    ....
  75. ncbi request reprint Cutting edge: cytotoxic granule polarization and cytolysis can occur without central supramolecular activation cluster formation in CD8+ effector T cells
    James P O'Keefe
    Committee on Cancer Biology, University of Chicago, IL 60637, USA
    J Immunol 175:5581-5. 2005
    ..Together, our results indicate that the formation of a cSMAC is not required for cytolytic activity in CD8+ effector T cells...
  76. ncbi request reprint A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma
    Amy C Peterson
    Department of Medicine, Section of Hematology Oncology, The University of Chicago, USA
    Invest New Drugs 24:141-9. 2006
    ..We combined different doses of Bryostatin-1 with IL-2 to determine effects on clinical response rate and T cell phenotype in patients with advanced kidney cancer...
  77. ncbi request reprint Update on vaccines for solid tumors
    Thomas F Gajewski
    University of Chicago, Chicago, IL 60637, USA
    Clin Adv Hematol Oncol 2:158-9. 2004
  78. ncbi request reprint Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8+ effector T cells
    Candace M Cham
    Committee on Cancer Biology, Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 174:4670-7. 2005
    ....
  79. ncbi request reprint Metabolic mechanisms of tumor resistance to T cell effector function
    Candace M Cham
    Department of Pathology, Department of Medicine, and the Ben May Institute, University of Chicago, Chicago, IL 60637, USA
    Immunol Res 31:107-18. 2005
    ..These observations provide a conceptual framework for modulating metabolic features of the T cell-tumor interaction, toward the end of promoting more effective immune-mediated tumor destruction in vivo...
  80. ncbi request reprint ICAM-1 contributes to but is not essential for tumor antigen cross-priming and CD8+ T cell-mediated tumor rejection in vivo
    Christian Blank
    Department of Pathology, Section of Hematology Oncology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 174:3416-20. 2005
    ..Our results suggest that ICAM-1 contributes to but is not absolutely required for CD8+ T cell-mediated tumor rejection in vivo and dominantly acts at the level of priming rather than the effector phase of the antitumor immune response...
  81. ncbi request reprint Tumor progression despite massive influx of activated CD8(+) T cells in a patient with malignant melanoma ascites
    Helena Harlin
    Department of Medicine, Section of Hematology Oncology, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA
    Cancer Immunol Immunother 55:1185-97. 2006
    ....
  82. ncbi request reprint On the TRAIL toward death receptor-based cancer therapeutics
    Thomas F Gajewski
    J Clin Oncol 25:1305-7. 2007
  83. ncbi request reprint T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
    Yuanyuan Zha
    Department of Pathology, Section of Hematology and Oncology, University of Chicago, Chicago, Illinois 60637, USA
    Nat Immunol 7:1166-73. 2006
    ..Our data support a causal function for excess DGK activity and defective Ras signaling in T cell anergy...
  84. ncbi request reprint Gene array and protein expression profiles suggest post-transcriptional regulation during CD8+ T cell differentiation
    Candace M Cham
    Committee on Cancer Biology, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 278:17044-52. 2003
    ....
  85. ncbi request reprint Innovations and challenges in melanoma: summary statement from the first Cambridge conference
    Michael B Atkins
    Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Clin Cancer Res 12:2291s-2296s. 2006
    ....
  86. ncbi request reprint Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results
    Brian I Rini
    University of California San Francisco, Comprehensive Cancer Center, San Francisco, CA 94115, USA
    J Clin Oncol 20:2017-24. 2002
    ..To evaluate the feasibility and safety of nonmyeloablative allogeneic stem-cell transplantation in patients with metastatic renal cell cancer (RCC) and to evaluate efficacy with respect to engraftment and tumor regression...
  87. ncbi request reprint Diagnosis and treatment of mycoplasma-contaminated cell cultures
    Helena Harlin
    University of Chicago, Chicago, Illinois, USA
    Curr Protoc Cytom . 2008
    ..This appendix describes how to test for mycoplasma contamination, and also presents methods for antibiotic treatment of infected cultures...
  88. ncbi request reprint Differential Ras signaling via the antigen receptor and IL-2 receptor in primary T lymphocytes
    Reinhard E Marks
    Department of Pathology, Department of Medicine Section of Hematology Oncology, The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA
    Biochem Biophys Res Commun 312:691-6. 2003
    ....
  89. pmc Molecular regulation of T-cell anergy
    Yan Zheng
    University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
    EMBO Rep 9:50-5. 2008
    ..A model is emerging for how these factors are regulated to control T-cell responsiveness...
  90. ncbi request reprint Phase II study of the Flk-1 tyrosine kinase inhibitor SU5416 in advanced melanoma
    Amy C Peterson
    Department of Medicine, Section of Hematology Oncology, University of Chicago Cancer Research Center, Chicago, Illinois, USA
    Clin Cancer Res 10:4048-54. 2004
    ..A Phase II study of SU5416, a preferential inhibitor of Flk-1, was carried out in patients with metastatic melanoma to determine clinical response, tolerability, and changes in tumor vascular perfusion...
  91. ncbi request reprint Semiquantitative analysis of dynamic contrast enhanced MRI in cancer patients: Variability and changes in tumor tissue over time
    Milica Medved
    Department of Radiology, The University of Chicago, Chicago, Illinois, USA
    J Magn Reson Imaging 20:122-8. 2004
    ..To evaluate variability of a simplified method for measuring semiquantitative DCE-MRI parameters in patients with cancer and to explore effects of treatment with a putative anti-angiogenic compound...
  92. ncbi request reprint Lymphoma-infiltrating immune cells
    Thomas F Gajewski
    N Engl J Med 352:724-5; author reply 724-5. 2005
  93. doi request reprint Diagnosis and treatment of Mycoplasma-contaminated cell cultures
    Helena Harlin
    University of Chicago, Chicago, Illinois, USA
    Curr Protoc Microbiol . 2006
    ..This appendix describes how to test for mycoplasma contamination, and also presents methods for antibiotic treatment of infected cultures...

Research Grants23

  1. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas Gajewski; Fiscal Year: 2007
    ..T cell transduction and tumor transfectants will be examined using factors identified to be useful from the TCR Tg model and mechanisms of improved tumor control will be dissected. ..
  2. Countering immune resistance in the melanoma tumor microenvironment
    Thomas F Gajewski; Fiscal Year: 2010
    ....
  3. Multi-Peptide/IL 12 Melanoma Vaccine
    Thomas Gajewski; Fiscal Year: 2003
    ..Understanding these mechanisms will illuminate the next level of intervention to develop to increase the clinical response to the immunotherapy of melanoma. ..
  4. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2004
    ....
  5. DGK in T Cell Regulation and Tolerance
    Thomas Gajewski; Fiscal Year: 2009
    ..Ti U,0 ._0 ... ur tow 5a' c' OUP O-0 N-0 0-0 V,12 oar aux. :E, -'1 .., (gyp afl' coo COD m='(Dm o03-' _=c 3m03 l17 CDG'O COB 111 ..
  6. Multi-Peptide/IL 12 Melanoma Vaccine
    Thomas Gajewski; Fiscal Year: 2006
    ..Understanding these mechanisms will illuminate the next level of intervention to develop to increase the clinical response to the immunotherapy of melanoma. ..
  7. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas F Gajewski; Fiscal Year: 2010
    ..T cell transduction and tumor transfectants will be examined using factors identified to be useful from the TCR Tg model and mechanisms of improved tumor control will be dissected. ..
  8. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2005
    ....
  9. Technologies To Block Gene Expression in Normal T Cells
    Thomas Gajewski; Fiscal Year: 2003
    ..abstract_text> ..
  10. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2003
    ....
  11. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2002
    ....
  12. Multi-Peptide/IL 12 Melanoma Vaccine
    Thomas Gajewski; Fiscal Year: 2004
    ..Understanding these mechanisms will illuminate the next level of intervention to develop to increase the clinical response to the immunotherapy of melanoma. ..
  13. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas Gajewski; Fiscal Year: 2009
    ..T cell transduction and tumor transfectants will be examined using factors identified to be useful from the TCR Tg model and mechanisms of improved tumor control will be dissected. ..
  14. Countering immune resistance in the melanoma tumor microenvironment
    Thomas Gajewski; Fiscal Year: 2009
    ....
  15. Biochemical/Molecular Changes Upon Naive T Cell Priming
    Thomas Gajewski; Fiscal Year: 2001
    ....
  16. Countering immune resistance in the melanoma tumor microenvironment
    Thomas Gajewski; Fiscal Year: 2007
    ....
  17. T Cell Responsiveness and Homeostasis in Anti-Tumor
    Thomas Gajewski; Fiscal Year: 2006
    ..T cell transduction and tumor transfectants will be examined using factors identified to be useful from the TCR Tg model and mechanisms of improved tumor control will be dissected. ..
  18. Molecular Dissection of T Cell Anergy
    Thomas Gajewski; Fiscal Year: 2005
    ..Ultimately, a complete understanding of the anergic state on the molecular level should guide the development of novel pharmacologic therapies to promote or reverse peripheral tolerance in vivo. ..
  19. Multi-Peptide/IL 12 Melanoma Vaccine
    Thomas Gajewski; Fiscal Year: 2005
    ..Understanding these mechanisms will illuminate the next level of intervention to develop to increase the clinical response to the immunotherapy of melanoma. ..
  20. DGK in T Cell Regulation and Tolerance
    Thomas F Gajewski; Fiscal Year: 2010
    ..Ti U,0 ._0 ... ur tow 5a' c' OUP O-0 N-0 0-0 V,12 oar aux. :E, -'1 .., (gyp afl' coo COD m='(Dm o03-' _=c 3m03 l17 CDG'O COB 111 ..