Thomas Gajewski

Summary

Affiliation: University of Chicago
Country: USA

Publications

  1. Luke J, Bao R, Sweis R, Spranger S, Gajewski T. WNT/β-catenin Pathway Activation Correlates with Immune Exclusion across Human Cancers. Clin Cancer Res. 2019;: pubmed publisher
    ..These data provide a strong rationale for development of pharmacologic inhibitors of this pathway with the aim of restoring immune cell infiltration and augmenting immunotherapy. ..
  2. Spaapen R, Leung M, Fuertes M, Kline J, Zhang L, Zheng Y, et al. Therapeutic activity of high-dose intratumoral IFN-β requires direct effect on the tumor vasculature. J Immunol. 2014;193:4254-60 pubmed publisher
    ..Our data help resolve conditions under which distinct antitumor mechanisms of type I IFNs are operational in vivo. ..
  3. Hantel A, Gabster B, Cheng J, GOLOMB H, Gajewski T. Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab. J Immunother Cancer. 2018;6:73 pubmed publisher
    ..Increasing use of regimens that include immune checkpoint inhibition require vigilant monitoring for immune-activating side effects as they can occasionally be life threatening, as in this case of HLH. ..
  4. Gajewski T, Louahed J, Brichard V. Gene signature in melanoma associated with clinical activity: a potential clue to unlock cancer immunotherapy. Cancer J. 2010;16:399-403 pubmed publisher
  5. Ascierto P, Atkins M, Bifulco C, Botti G, COCHRAN A, Davies M, et al. Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014. J Transl Med. 2015;13:374 pubmed publisher
    ..Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma. ..
  6. Sivan A, Corrales L, Hubert N, Williams J, Aquino Michaels K, Earley Z, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084-9 pubmed publisher
    ..Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy. ..
  7. Gajewski T. The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment. Semin Oncol. 2015;42:663-71 pubmed publisher
    ..It is envisioned that the end result of these investigations will be an expanded array of interventions that will broaden the fraction of patients benefitting from immunotherapies in the clinic. ..
  8. Gajewski T, Corrales L. New perspectives on type I IFNs in cancer. Cytokine Growth Factor Rev. 2015;26:175-8 pubmed publisher
    ..However, high doses of intratumoral type I IFNs largely function via an anti-angiogenic effect. Understanding these mechanistic details should enable improved clinical manipulation of the type I IFN system in cancer. ..
  9. request reprint
    Gajewski T. The expanding universe of regulatory T cell subsets in cancer. Immunity. 2007;27:185-7 pubmed
    ..In this issue of Immunity, Peng et al. (2007) add to this list by describing tumor-infiltrating gammadelta T cells that have regulatory function. ..

More Information

Publications22

  1. Woo S, Corrales L, Gajewski T. The STING pathway and the T cell-inflamed tumor microenvironment. Trends Immunol. 2015;36:250-6 pubmed publisher
    ..Knowledge of this pathway is guiding the further development of novel immunotherapeutic strategies. ..
  2. Corrales L, Gajewski T. Molecular Pathways: Targeting the Stimulator of Interferon Genes (STING) in the Immunotherapy of Cancer. Clin Cancer Res. 2015;21:4774-9 pubmed publisher
  3. Spranger S, Sivan A, Corrales L, Gajewski T. Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy. Adv Immunol. 2016;130:75-93 pubmed publisher
    ..Successful identification of such causal factors should lead to new therapeutic approaches that may facilitate T cell entry into noninflamed tumors and expand the fraction of patients capable of responding to novel immunotherapies. ..
  4. Corrales L, Glickman L, McWhirter S, Kanne D, Sivick K, Katibah G, et al. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity. Cell Rep. 2015;11:1018-30 pubmed publisher
    ..Synthetic CDNs have high translational potential as a cancer therapeutic. ..
  5. Corrales L, Woo S, Williams J, McWhirter S, Dubensky T, Gajewski T. Antagonism of the STING Pathway via Activation of the AIM2 Inflammasome by Intracellular DNA. J Immunol. 2016;196:3191-8 pubmed publisher
    ..Our data suggest that in vitro activation of the AIM2 inflammasome in murine macrophages and dendritic cells leads to reduced activation of the STING pathway, in part through promoting caspase-1-dependent cell death. ..
  6. Spranger S, Luke J, Bao R, Zha Y, Hernandez K, Li Y, et al. Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma. Proc Natl Acad Sci U S A. 2016;113:E7759-E7768 pubmed
    ..Strategies that improve T-cell infiltration into tumors may therefore be able to facilitate clinical response to immunotherapy once antigens become recognized. ..
  7. Fessler J, Gajewski T. The Microbiota: A New Variable Impacting Cancer Treatment Outcomes. Clin Cancer Res. 2017;23:3229-3231 pubmed publisher
    ..i>Clin Cancer Res; 23(13); 3229-31. ©2017 AACRSee related article by Galloway-Peña et al., p. 3263. ..
  8. Williams J, Horton B, Zheng Y, Duan Y, Powell J, Gajewski T. The EGR2 targets LAG-3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8+ T cells in the tumor microenvironment. J Exp Med. 2017;214:381-400 pubmed publisher
    ..Our results indicate that coexpression of LAG-3 and 4-1BB characterize dysfunctional T cells within tumors, and that targeting these receptors has therapeutic utility. ..
  9. Spranger S, Dai D, Horton B, Gajewski T. Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy. Cancer Cell. 2017;31:711-723.e4 pubmed publisher
    ..Our data indicate that lack of CD103+ DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape. ..
  10. Woo S, Fuertes M, Corrales L, Spranger S, Furdyna M, Leung M, et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41:830-42 pubmed publisher
    ..Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy. ..
  11. request reprint
    Gajewski T, Fallarino F, Fields P, Rivas F, Alegre M. 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. J Immunol. 2001;166:3900-7 pubmed
    ..Thus, the biochemical mechanism explaining the differential inhibitory effect of CTLA-4 on naive and primed CD8(+) T cells remains unclear. ..
  12. Sweis R, Spranger S, Bao R, Paner G, Stadler W, Steinberg G, et al. Molecular Drivers of the Non-T-cell-Inflamed Tumor Microenvironment in Urothelial Bladder Cancer. Cancer Immunol Res. 2016;4:563-8 pubmed publisher
    ..The three pathways identified represent targetable potential pathways of tumor-intrinsic immunotherapy resistance. Cancer Immunol Res; 4(7); 563-8. ©2016 AACR. ..
  13. Horton B, Williams J, Cabanov A, Spranger S, Gajewski T. Intratumoral CD8+ T-cell Apoptosis Is a Major Component of T-cell Dysfunction and Impedes Antitumor Immunity. Cancer Immunol Res. 2018;6:14-24 pubmed publisher
    ..i>Cancer Immunol Res; 6(1); 14-24. ©2017 AACR. ..