tumor escape


Summary: The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (CD28 ANTIGENS) and CD80 antigens (B7-1 ANTIGEN).

Top Publications

  1. Wei J, Wang F, Kong L, Xu S, Doucette T, Ferguson S, et al. miR-124 inhibits STAT3 signaling to enhance T cell-mediated immune clearance of glioma. Cancer Res. 2013;73:3913-26 pubmed publisher
    ..Our findings highlight the potential application of miR-124 as a novel immunotherapeutic agent for neoplasms and serve as a model for identifying miRNAs that can be exploited as immunotherapeutics...
  2. Bernal M, Ruiz Cabello F, Concha A, Paschen A, Garrido F. Implication of the ?2-microglobulin gene in the generation of tumor escape phenotypes. Cancer Immunol Immunother. 2012;61:1359-71 pubmed publisher
    ..It also summarizes recent studies that point to an acquired ?2m deficiency in response to cancer immunotherapy, a barrier to successful vaccination or adoptive cellular therapy. ..
  3. Zhou G, Levitsky H. Towards curative cancer immunotherapy: overcoming posttherapy tumor escape. Clin Dev Immunol. 2012;2012:124187 pubmed publisher
  4. Pietra G, Manzini C, Rivara S, Vitale M, Cantoni C, Petretto A, et al. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res. 2012;72:1407-15 pubmed publisher
    ..adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function...
  5. Yang D, Torres C, Bardhan K, Zimmerman M, McGaha T, Liu K. Decitabine and vorinostat cooperate to sensitize colon carcinoma cells to Fas ligand-induced apoptosis in vitro and tumor suppression in vivo. J Immunol. 2012;188:4441-9 pubmed publisher
    ..Thus, our data suggest that combined modalities of chemotherapy to sensitize the tumor cell to Fas-mediated apoptosis and CTL immunotherapy is an effective approach for the suppression of colon cancer metastasis...
  6. Umansky V, Sevko A. Melanoma-induced immunosuppression and its neutralization. Semin Cancer Biol. 2012;22:319-26 pubmed publisher
  7. Shanker A, Marincola F. Cooperativity of adaptive and innate immunity: implications for cancer therapy. Cancer Immunol Immunother. 2011;60:1061-74 pubmed publisher
    ..Mechanistic understanding of this two-way immune cross-talk could provide insights into novel strategies for designing better immunotherapy approaches against cancer and other diseases that normally defy immune control. ..
  8. Lu T, Ramakrishnan R, Altiok S, Youn J, Cheng P, Celis E, et al. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest. 2011;121:4015-29 pubmed publisher
    ..Our data therefore suggest what we believe to be a novel mechanism of MDSC-mediated tumor cell resistance to CTLs. ..
  9. Hirschhaeuser F, Sattler U, Mueller Klieser W. Lactate: a metabolic key player in cancer. Cancer Res. 2011;71:6921-5 pubmed publisher
    ..In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology. ..

More Information


  1. Janikashvili N, Bonnotte B, Katsanis E, Larmonier N. The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance. Clin Dev Immunol. 2011;2011:430394 pubmed publisher
    ..Herein we review these bidirectional communications between DCs and Treg as they relate to the promotion of cancer-induced tolerance. ..
  2. Lesokhin A, Hohl T, Kitano S, Cortez C, Hirschhorn Cymerman D, Avogadri F, et al. Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res. 2012;72:876-86 pubmed publisher
    ..Our results argue that therapeutic targeting of monocytic MDSCs would enhance outcomes in immunotherapy. ..
  3. Woo S, Turnis M, Goldberg M, Bankoti J, Selby M, Nirschl C, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012;72:917-27 pubmed publisher
    ..In addition, they argue strongly that dual blockade of these molecules represents a promising combinatorial strategy for cancer. ..
  4. Choi S, Gout P, Collins C, Wang Y. Epithelial immune cell-like transition (EIT): a proposed transdifferentiation process underlying immune-suppressive activity of epithelial cancers. Differentiation. 2012;83:293-8 pubmed publisher
    ..This proposed paradigm shift could lead to novel therapeutic approaches with improved efficacy and broad application. ..
  5. Jadus M, Natividad J, Mai A, Ouyang Y, Lambrecht N, Szabo S, et al. Lung cancer: a classic example of tumor escape and progression while providing opportunities for immunological intervention. Clin Dev Immunol. 2012;2012:160724 pubmed publisher
    ..This paper will cover the escape mechanisms of bronchogenic lung cancer that must be overcome before they can be successfully treated. We also review the history of immunotherapy directed towards lung cancers. ..
  6. Villalba M, Rathore M, López Royuela N, Krzywinska E, Garaude J, Allende Vega N. From tumor cell metabolism to tumor immune escape. Int J Biochem Cell Biol. 2013;45:106-13 pubmed publisher
    ..This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. ..
  7. Kaluza K, Kottke T, Diaz R, Rommelfanger D, Thompson J, Vile R. Adoptive transfer of cytotoxic T lymphocytes targeting two different antigens limits antigen loss and tumor escape. Hum Gene Ther. 2012;23:1054-64 pubmed publisher
    ..against two independent antigens would reduce selection for single-antigen-loss cells, thereby limiting tumor escape. Using OT-I and Pmel T cells to treat B16ova tumors, we found that early cotransfer could prevent tumor ..
  8. Mussai F, De Santo C, Cerundolo V. Interaction between invariant NKT cells and myeloid-derived suppressor cells in cancer patients: evidence and therapeutic opportunities. J Immunother. 2012;35:449-59 pubmed publisher
    ..This review discusses the evidence for MDSCs in tumor progression and the implication that iNKT cells could be developed as a potent therapeutic strategy. ..
  9. Suzuki Y, Sutoh M, Hatakeyama S, Mori K, Yamamoto H, Koie T, et al. MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis. Int J Oncol. 2012;40:1831-8 pubmed publisher
    ..We reveal that MUC1 carrying core 2 O-glycans thus functions as a molecular shield against NK cell attack, thereby promoting bladder tumor metastasis. ..
  10. Poschke I, Mougiakakos D, Kiessling R. Camouflage and sabotage: tumor escape from the immune system. Cancer Immunol Immunother. 2011;60:1161-71 pubmed publisher
    ..Evaluation of anti-tumor immunity in such trials as well as in animal models has shown that tumor escape from immune recognition and tumor-mediated suppression of anti-tumor immunity can pose a significant obstacle ..
  11. Cheng C, Qu Q, Shen Y, Lv Y, Zhu Y, Zhang X, et al. Overexpression of B7-H4 in tumor infiltrated dendritic cells. J Immunoassay Immunochem. 2011;32:353-64 pubmed publisher
    ..These data indicate that tumor environment may condition local DCs to become dysfunctional in the phenotype, and that the high expression of B7-H4 may contribute to the tumor infiltrated DCs to mediate immune invasion. ..
  12. Sapoznik S, Hammer O, Ortenberg R, Besser M, Ben Moshe T, Schachter J, et al. Novel anti-melanoma immunotherapies: disarming tumor escape mechanisms. Clin Dev Immunol. 2012;2012:818214 pubmed publisher
    ..This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles. ..
  13. Delfortrie S, Pinte S, Mattot V, Samson C, Villain G, Caetano B, et al. Egfl7 promotes tumor escape from immunity by repressing endothelial cell activation. Cancer Res. 2011;71:7176-86 pubmed publisher
    ..Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control. ..
  14. Godin Ethier J, Hanafi L, Piccirillo C, Lapointe R. Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res. 2011;17:6985-91 pubmed publisher
    ..Consequently, IDO inhibition seems a promising approach for cancer immunotherapy. ..
  15. Seidel U, Oliveira C, Lampen M, Hall T. A novel category of antigens enabling CTL immunity to tumor escape variants: Cinderella antigens. Cancer Immunol Immunother. 2012;61:119-25 pubmed publisher
    ..TEIPP-specific CTLs and their cognate peptide-epitopes provide a new strategy to counteract immune evasion by APM defects and bear potential to targeting escape variants observed in a wide range of cancers. ..
  16. Montero A, DIAZ MONTERO C, Kyriakopoulos C, Bronte V, Mandruzzato S. Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother. 2012;35:107-15 pubmed publisher
    ..Finally, we examine the strategies designed to modulate MDSCs in cancer patients, which might represent an innovative approach to enhance the effectiveness of immune-based therapies. ..
  17. Waldhauer I, Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008;27:5932-43 pubmed publisher
  18. Di Carlo E, D Antuono T, Pompa P, Giuliani R, Rosini S, Stuppia L, et al. The lack of epithelial interleukin-7 and BAFF/BLyS gene expression in prostate cancer as a possible mechanism of tumor escape from immunosurveillance. Clin Cancer Res. 2009;15:2979-87 pubmed publisher
    ..Its loss in PCa is associated with a severe depletion of prostate-associated lymphocytes and points to a novel tumor escape mechanism.
  19. Whiteside T, Mandapathil M, Szczepanski M, Szajnik M. Mechanisms of tumor escape from the immune system: adenosine-producing Treg, exosomes and tumor-associated TLRs. Bull Cancer. 2011;98:E25-31 pubmed publisher
    ..b>Tumor escape has been a major problem in cancer immunotherapy and it has been held responsible for the failure of many ..
  20. Yaguchi T, Sumimoto H, Kudo Saito C, Tsukamoto N, Ueda R, Iwata Kajihara T, et al. The mechanisms of cancer immunoescape and development of overcoming strategies. Int J Hematol. 2011;93:294-300 pubmed publisher
    ..Therefore, targeting these signals both in cancer cells and immunosuppressive immune cells may result in the restoration of immunocompetence in cancer patients and improve current immunotherapy. ..
  21. Yasumoto K, Hanagiri T, Takenoyama M. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer. Gen Thorac Cardiovasc Surg. 2009;57:449-57 pubmed publisher
    ..b>Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy...
  22. Zhou Q, Bucher C, Munger M, Highfill S, Tolar J, Munn D, et al. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 2009;114:3793-802 pubmed publisher
  23. Badoual C, Sandoval F, Pere H, Hans S, Gey A, Merillon N, et al. Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies. Head Neck. 2010;32:946-58 pubmed publisher
    ..Only a better understanding of this tumor-host interaction will permit a rational design of new immunotherapeutic approaches combining immunostimulation with drugs endowed with the ability to counteract immunoevasion mechanisms. ..
  24. Lesport E, Baudhuin J, Lemaoult J, Sousa S, Doliger C, Carosella E, et al. Human melanoma cell secreting human leukocyte antigen-G5 inhibit natural killer cell cytotoxicity by impairing lytic granules polarization toward target cell. Hum Immunol. 2009;70:1000-5 pubmed publisher
    ..These results highlight the inhibitory mechanisms mediated through HLA-G5 leading to tumor escape from NK cell cytotoxicity.
  25. Coe D, Addey C, White M, Simpson E, Dyson J, Chai J. The roles of antigen-specificity, responsiveness to transforming growth factor-? and antigen-presenting cell subsets in tumour-induced expansion of regulatory T cells. Immunology. 2010;131:556-69 pubmed publisher
    ..This study not only provides an in vivo system in which cross-talk between nTreg cells and tumours can be explored but also reveals novel aspects of tumour immune evasion. ..
  26. Szajnik M, Szczepanski M, Czystowska M, Elishaev E, Mandapathil M, Nowak Markwitz E, et al. TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer. Oncogene. 2009;28:4353-63 pubmed publisher
    ..In PTX-sensitive, MyD88(neg) A2780 cells, TLR4 stimulation upregulated TRIF, and TLR4 silencing eliminated this effect. Thus, TLR4/MyD88 signaling supports OvCa progression and chemoresistance, promoting immune escape. ..
  27. Zhang L, Gajewski T, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114:1545-52 pubmed publisher
    ..These data suggest the importance of the PD-1/PD-L1 pathway in immune evasion by a hematologic malignancy, providing a rationale for clinical trials targeting this pathway in leukemia patients. ..
  28. Stewart T, Abrams S. How tumours escape mass destruction. Oncogene. 2008;27:5894-903 pubmed publisher
  29. Ramos C, Dotti G. Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy. Expert Opin Biol Ther. 2011;11:855-73 pubmed publisher
    ..Because of recent advances in immunology, genetics and cell processing, CAR-modified T cells will likely play an increasing role in the cellular therapy of cancer, chronic infections and autoimmune disorders. ..
  30. Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene. 2008;27:5869-85 pubmed publisher
    ..Therefore, strategies to overcome epigenetic modifications underlying changes in HLA antigen expression in malignant cells have been discussed. ..
  31. Schreiber R, Old L, Smyth M. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331:1565-70 pubmed publisher
    ..Here, we discuss a unifying conceptual framework called "cancer immunoediting," which integrates the immune system's dual host-protective and tumor-promoting roles. ..
  32. Koido S, Homma S, Hara E, Namiki Y, Takahara A, Komita H, et al. Regulation of tumor immunity by tumor/dendritic cell fusions. Clin Dev Immunol. 2010;2010:516768 pubmed publisher
    ..This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment. ..
  33. Wei S, Shreiner A, Takeshita N, Chen L, Zou W, Chang A. Tumor-induced immune suppression of in vivo effector T-cell priming is mediated by the B7-H1/PD-1 axis and transforming growth factor beta. Cancer Res. 2008;68:5432-8 pubmed publisher
    ..These results show a major role for the B7-H1/PD-1 axis and TGF-beta as synergistic suppressive mechanisms in cTDLN. Our data have clinical relevance in the generation of effector T cells in the tumor-bearing host. ..
  34. Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, et al. Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother. 2011;60:639-48 pubmed publisher
    ..Taken together, these data point to the fact that tumour-derived exosomes interfere with the tumour-specific function of immune cells and constitute an additional mechanism how tumours escape from immune surveillance. ..
  35. Ahmadzadeh M, Johnson L, Heemskerk B, Wunderlich J, Dudley M, White D, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114:1537-44 pubmed publisher
    ..These findings suggest that the tumor microenvironment can lead to up-regulation of PD-1 on tumor-reactive T cells and contribute to impaired antitumor immune responses. ..
  36. Zhao F, Falk C, Osen W, Kato M, Schadendorf D, Umansky V. Activation of p38 mitogen-activated protein kinase drives dendritic cells to become tolerogenic in ret transgenic mice spontaneously developing melanoma. Clin Cancer Res. 2009;15:4382-90 pubmed publisher
    ..We suggest that new strategies of melanoma immunotherapy can include inhibitors of p38 MAPK activity in DCs. ..
  37. Wieckowski E, Visus C, Szajnik M, Szczepanski M, Storkus W, Whiteside T. Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immunol. 2009;183:3720-30 pubmed publisher
    ..The data suggest that tumor-derived MV induce immune suppression by promoting T regulatory cell expansion and the demise of antitumor CD8(+) effector T cells, thus contributing to tumor escape.
  38. Liao Y, Wang C, Schaue D, Iwamoto K, McBride W. Local irradiation of murine melanoma affects the development of tumour-specific immunity. Immunology. 2009;128:e797-804 pubmed publisher
  39. Palucka A, Ueno H, Fay J, Banchereau J. Dendritic cells: a critical player in cancer therapy?. J Immunother. 2008;31:793-805 pubmed publisher
  40. Lin A, Schildknecht A, Nguyen L, Ohashi P. Dendritic cells integrate signals from the tumor microenvironment to modulate immunity and tumor growth. Immunol Lett. 2010;127:77-84 pubmed publisher
  41. Liu J, Lu G, Tang F, Liu Y, Cui G. Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell carcinomas. Virchows Arch. 2009;455:441-8 pubmed publisher
    ..factors derived from the tumor and nontumor cells present in the tumor microenvironment contribute to tumor escape from host immune attack...
  42. Mu C, Huang J, Chen Y, Chen C, Zhang X. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011;28:682-8 pubmed publisher
  43. Belov K. The role of the Major Histocompatibility Complex in the spread of contagious cancers. Mamm Genome. 2011;22:83-90 pubmed publisher
    ..Transmissible cancers are rare but they can provide unique insights into the genetics and immunology of tumours and organ transplants...
  44. Kmieciak M, Payne K, Idowu M, Grimes M, Graham L, Ascierto M, et al. Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure. J Transl Med. 2011;9:35 pubmed publisher
  45. Holmes T, El Sherbiny Y, Davison A, Clough S, Blair G, Cook G. A human NK cell activation/inhibition threshold allows small changes in the target cell surface phenotype to dramatically alter susceptibility to NK cells. J Immunol. 2011;186:1538-45 pubmed publisher
    ..Whereas this allows for the efficient detection of target cells, it also provides a route for pathogens and tumors to evade NK cell attack. ..
  46. Ahmed N, Salsman V, Kew Y, Shaffer D, Powell S, Zhang Y, et al. HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors. Clin Cancer Res. 2010;16:474-85 pubmed publisher
    ..Hence, the adoptive transfer of HER2-redirected T cells may be a promising immunotherapeutic approach for GBM. ..
  47. Aldinucci D, Gloghini A, Pinto A, De Filippi R, Carbone A. The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escape. J Pathol. 2010;221:248-63 pubmed publisher
  48. Champsaur M, Lanier L. Effect of NKG2D ligand expression on host immune responses. Immunol Rev. 2010;235:267-85 pubmed publisher
    ..We also discuss the host response to both membrane-bound and secreted NKG2D ligands and summarize the models proposed to explain the consequences of this differential expression. ..
  49. Arum C, Anderssen E, Viset T, Kodama Y, Lundgren S, Chen D, et al. Cancer immunoediting from immunosurveillance to tumor escape in microvillus-formed niche: a study of syngeneic orthotopic rat bladder cancer model in comparison with human bladder cancer. Neoplasia. 2010;12:434-42 pubmed
    ..We suggest that the microvillus-formed niche that harbors a few implanted cancer cells might be the compartment that prevents the tumor eradication by the host immune system...
  50. Horkheimer I, Quigley M, Zhu J, Huang X, Chao N, Yang Y. Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation. Blood. 2009;113:5330-9 pubmed publisher
    ..Collectively, these results may suggest effective immunotherapeutic strategies for treating cancer after stem cell transplantation. ..
  51. Uppaluri R, Dunn G, Lewis J. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers. Cancer Immun. 2008;8:16 pubmed
    ..Finally, with this perspective, we describe our current understanding of tumor infiltrating lymphocyte data for head and neck cancers...
  52. Quezada S, Peggs K, Simpson T, Allison J. Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol Rev. 2011;241:104-18 pubmed publisher
    ..Finally, we also discuss work associated to the manipulation of the immune response to tumors and its impact on the infiltration, accumulation, and function of tumor-reactive lymphocytes within the tumor microenvironment. ..
  53. Campoli M, Ferrone S. Tumor escape mechanisms: potential role of soluble HLA antigens and NK cells activating ligands. Tissue Antigens. 2008;72:321-34 pubmed publisher