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Cancer Induced Immunosuppression and Its Modulation by Signal Inhibitors

  • Chapter
Resistance of Cancer Cells to CTL-Mediated Immunotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 7))

  • 932 Accesses

Abstract

Although cancer immunotherapy has recently demonstrated durable responses even in patients with advanced cancer, not all patients or cancer types respond to the therapy. Pretreatment immune status varies among cancer patients and is correlated with responses to immunotherapy. Immune conditions may be defined by the balance of positive and negative pathways in the anti-tumor immune responses, which are regulated by both cancer cell characteristics and patients’ immune-reactivity along with various environmental factors. Gene alterations and signal activation define the immunological characteristics of cancer cells; tumor specific peptides derived from passenger mutations induce anti-tumor T-cells and oncogene activation (e.g. driver mutations, overexpression: MAPK, STAT3, NF-κB, β-catenin) rather promote immunosuppression. Oncogene/signal activation in cancer cells triggers multiple immunosuppressive cascades involving various immunosuppressive molecules and cells (e.g. TGF-β, IL10, IL6, VEGF, Treg, MDSC). Signal inhibitors are able to augment anti-tumor T-cell responses through multiple mechanisms including inhibition of cancer-induced immunosuppression, immunogenic cancer cell death, and enhancement of immune cell functions. Since the oncogene-signal activation status is different among patients, personalized immunotherapy combined with appropriate signal inhibitors may be considered for the development of effective immunotherapy.

No potential conflicts of interest were disclosed.

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Abbreviations

ACT:

Adoptive cell therapy

CAF:

Cancer associated fibroblast

CAR:

Chimeric antigen receptor

CTL:

Cytotoxic T lymphocyte

DC:

Dendritic cell

EMT:

Epithelial to mesenchymal transition

MDSC:

Myeloid derived suppressor cells

MSI:

Microsatellite instability

pDC:

Plasmacytoid DC

TCR:

T-cell receptor

Tfh:

Follicular helper T-cells

TIL:

Tumor infiltrating T-cells

Treg:

Regulatory T-cells

References

  1. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.

    Article  CAS  PubMed  Google Scholar 

  2. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2455–65.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17:4550–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011;29:917–24.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3:95.

    Article  Google Scholar 

  7. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4:127.

    Article  Google Scholar 

  8. Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306.

    Article  CAS  PubMed  Google Scholar 

  9. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D'Arrigo C, Vidal-Vanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pagès F. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Kawakami Y, Rosenberg SA. Human tumor antigens recognized by T cells. Immunol Res. 1997;16:313–39.

    Article  CAS  PubMed  Google Scholar 

  11. Kawakami Y, Fujita T, Matsuzaki Y, Sakurai T, Tsukamoto M, Toda M, Sumimoto H. Identification of human tumor antigens and its implications for diagnosis and treatment of cancer. Cancer Sci. 2004;95:784–91.

    Article  CAS  PubMed  Google Scholar 

  12. Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994;91:3515–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Robbins PF, El-Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA. A mutated b2-catenin gene encodes a melanoma – specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med. 1996;183:1185–92.

    Article  CAS  PubMed  Google Scholar 

  14. Kawakami Y, Wang X, Shofuda T, Sumimoto H, Tupesis J, Fitzgerald E, Rosenberg S. Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor infiltrating T lymphocytes. J Immunol. 2001;166:2871–7.

    Article  CAS  PubMed  Google Scholar 

  15. Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med. 2013;19:747–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Ishikawa T, Fujita T, Suzuki Y, Okabe S, Yuasa Y, Iwai T, Kawakami Y. Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability. Cancer Res. 2003;63:5564–72.

    CAS  PubMed  Google Scholar 

  17. Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, Bruneval P, Fridman WH, Becker C, Pagès F, Speicher MR, Trajanoski Z, Galon J. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39:782–95.

    Article  CAS  PubMed  Google Scholar 

  18. Mlecnik B, Bindea G, Angell HK, Sasso MS, Obenauf AC, Fredriksen T, Lafontaine L, Bilocq AM, Kirilovsky A, Tosolini M, Waldner M, Berger A, Fridman WH, Rafii A, Valge-Archer V, Pagès F, Speicher MR, Galon J. Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients. Sci Transl Med. 2014;6:228.

    Article  Google Scholar 

  19. Nakamura S, Yaguchi T, Kawamura N, Kobayashi A, Sakurai T, Higuchi H, Takaishi H, Hibi T, Kawakami Y. TGF-β1 in tumor microenvironments induces immunosuppression in the tumors and sentinel lymph nodes and promotes tumor progression. J Immunother. 2014;37:63–72.

    Article  CAS  PubMed  Google Scholar 

  20. Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y. Cancer metastasis is accelerated through immunosuppression during EMT of cancer cell. Cancer Cell. 2009;15:195–206.

    Article  CAS  PubMed  Google Scholar 

  21. Kudo-Saito C, Shirako H, Ohike M, Tsukamoto N, Kawakami Y. CCL2 is critical for immunosuppression to promote cancer metastasis. Clin Exp Metastasis. 2013;30:393–405.

    Article  CAS  PubMed  Google Scholar 

  22. Tsujikawa T, Yaguchi T, Ohmura G, Ohta S, Kobayashi A, Kawamura N, Fujita T, Nakano H, Shimada T, Takahashi T, Nakao R, Yanagisawa A, Hisa Y, Kawakami Y. Autocrine and paracrine loops between cancer cells and macrophages promote lymph node metastasis via CCR4/CCL22 in head and neck squamous cell carcinoma. Int J Cancer. 2012;132:2755–66.

    Article  PubMed  Google Scholar 

  23. Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Ueda R, Iwata-Kajihara T, Nishio H, Kawamura N, Kawakami Y. The mechanisms of cancer immunoescape and development of overcoming strategies. Int J Hematol. 2011;93:294–300.

    Article  PubMed  Google Scholar 

  24. Sumimoto H, Miyagishi M, Miyoshi H, Yamagata S, Shimizu A, Taira K, Kawakami Y. Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference. Oncogene. 2004;23:6031–9.

    Article  CAS  PubMed  Google Scholar 

  25. Sumimoto H, Imabayashi F, Iwata T, Kawakami Y. The BRAF-MAPK signaling pathway is essential for cancer immune evasion in human melanoma cells. J Exp Med. 2006;203:1651–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Kono M, Dunn IS, Durda PJ, Butera D, Rose LB, Haggerty TJ, Benson EM, Kurnick JT. Role of the mitogen-activated protein kinase signaling pathway in the regulation of human melanocytic antigen expression. Mol Cancer Res. 2006;4:779–92.

    Article  CAS  PubMed  Google Scholar 

  27. Hong DS, Vence L, Falchook G, Radvanyi LG, Liu C, Goodman V, Legos JJ, Blackman S, Scarmadio A, Kurzrock R, Lizee G, Hwu P. BRAF(V600) inhibitor GSK2118436 targeted inhibition of mutant BRAF in cancer patients does not impair overall immune competency. Clin Cancer Res. 2012;18:2326–35.

    Article  CAS  PubMed  Google Scholar 

  28. Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CN, Sloss CM, Ferrone CR, Flaherty KT, Lawrence DP, Fisher DE, Tsao H, Wargo JA. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 2010;70:5213–9.

    Article  CAS  PubMed  Google Scholar 

  29. Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P, Scolyer RA. Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 2012;18:1386–94.

    Article  CAS  PubMed  Google Scholar 

  30. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  31. Iwata-Kajihara T, Sumimoto H, Kawamura N, Ueda R, Takahashi T, Mizuguchi H, Miyagishi M, Takeda K, Kawakami Y. Enhanced cancer immunotherapy using STAT3-depleted dendritic cells with high Th1-inducing ability and resistance to cancer cell-derived inhibitory factors. J Immunol. 2011;187:27–36.

    Article  CAS  PubMed  Google Scholar 

  32. Wu L, Du H, Li Y, Qu P, Yan C. Signal transducer and activator of transcription 3 (Stat3C) promotes myeloid-derived suppressor cell expansion and immune suppression during lung tumorigenesis. Am J Pathol. 2011;179:2131–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Poschke I, Mougiakakos D, Hansson J, Masucci GV, Kiessling R. Immature immunosuppressive CD14 + HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res. 2010;70:4335–45.

    Article  CAS  PubMed  Google Scholar 

  34. Pallandre JR, Brillard E, Créhange G, Radlovic A, Remy-Martin JP, Saas P, Rohrlich PS, Pivot X, Ling X, Tiberghien P, Borg C. Role of STAT3 in CD4 + CD25 + FOXP3+ regulatory lymphocyte generation: implications in graft-versus-host disease and antitumor immunity. J Immunol. 2007;179:7593–604.

    Article  CAS  PubMed  Google Scholar 

  35. Kujawski M, Zhang C, Herrmann A, Reckamp K, Scuto A, Jensen M, Deng J, Forman S, Figlin R, Yu H. Targeting STAT3 in adoptively transferred T cells promotes their in vivo expansion and antitumor effects. Cancer Res. 2010;70:9599–610.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Lee H, Pal SK, Reckamp K, Figlin RA, Yu H. STAT3: a target to enhance antitumor immune response. Curr Top Microbiol Immunol. 2011;344:41–59.

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Burdelya L, Catlett-Falcone R, Levitzki A, Cheng F, Mora LB, Sotomayor E, Coppola D, Sun J, Sebti S, Dalton WS, Jove R, Yu H. Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone. Mol Cancer Ther. 2002;1:893–9.

    CAS  PubMed  Google Scholar 

  38. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, Dreicer R, Bukowski R, Finke JH. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15:2148–57.

    Article  CAS  PubMed  Google Scholar 

  39. Jalkanen SE, Vakkila J, Kreutzman A, Nieminen JK, Porkka K, Mustjoki S. Poor cytokine-induced phosphorylation in chronic myeloid leukemia patients at diagnosis is effectively reversed by tyrosine kinase inhibitor therapy. Exp Hematol. 2011;39:102–13.

    Article  CAS  PubMed  Google Scholar 

  40. Nishio H, Yaguchi T, Sugiyama J, Sumimoto H, Umezawa K, Iwata T, Susumu N, Fujii T, Kawamura N, Kobayashi A, Park J, Aoki D, Kawakami Y. Immunosuppression through constitutively activated NF-κB signaling in human ovarian cancer and its reversal by a NF-κB inhibitor. Br J Cancer. 2014;110:2965–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Tsukamoto N, Okada S, Onami Y, Sasaki Y, Umezawa K, Kawakami Y. Impairment of plasmacytoid dendritic cells for IFN production by the ligand for immunoglobulin-like transcript 7 expressed on human cancer cells. Clin Cancer Res. 2009;15:5733–43.

    Article  CAS  PubMed  Google Scholar 

  42. Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, Mischel PS, Stokoe D, Pieper RO. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007;13:84–8.

    Article  CAS  PubMed  Google Scholar 

  43. Yaguchi T, Goto Y, Kido K, Mochimaru H, Sakurai T, Tsukamoto N, Kudo-Saito C, Fujita T, Sumimoto H, Kawakami Y. Immune suppression and resistance mediated by constitutive activation of Wnt/β-catenin signaling in human melanoma cells. J Immunol. 2012;189:2110–7.

    Article  CAS  PubMed  Google Scholar 

  44. Fu C, Jiang A. Generation of tolerogenic dendritic cells via the E-cadherin/β-catenin-signaling pathway. Immunol Res. 2010;46:72–8.

    Article  CAS  PubMed  Google Scholar 

  45. Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez RM, Wang YC, Pulendran B. Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010;329:849–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Ding Y, Shen S, Lino AC, Curotto de Lafaille MA, Lafaille JJ. Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells. Nat Med. 2008;14:162–9.

    Google Scholar 

  47. Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, Kawakami Y, Seipp CA, Einhorn JH, White DE. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med. 1998;4:321–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Salgaller ML, Afshar A, Marincola FM, Rivoltini L, Kawakami Y, Rosenberg SA. Recognition of multiple epitopes in the human melanoma antigen gp100 by antigen specific peripheral blood lymphocytes stimulated with synthetic peptides. Cancer Res. 1995;55:4972–9.

    CAS  PubMed  Google Scholar 

  49. Ueda R, Ohkusu-Tsukada K, Fusaki N, Soeda A, Kawase T, Kawakami Y, Toda M. Identification of HLA-A2- and A24-restricted T-cell epitopes derived from SOX6 expressed in glioma stem cells for immunotherapy. Int J Cancer. 2010;126:919–29.

    CAS  PubMed  Google Scholar 

  50. Toda M, Iizuka Y, Kawase T, Uyemura K, Kawakami Y. Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV. Cancer Gene Ther. 2002;9:356–64.

    Article  CAS  PubMed  Google Scholar 

  51. Ohkusu-Tsukada K, Ohta S, Kawakami Y, Toda M. Adjuvant effects of formalin-inactivated HSV through activation of dendritic cells and inactivation of myeloid-derived suppressor cells in cancer immunotherapy. Int J Cancer. 2011;128:119–31.

    Article  CAS  PubMed  Google Scholar 

  52. Udagawa M, Kudo-Saito C, Hasegawa G, Yano K, Yamamoto A, Yaguchi M, Toda M, Azuma I, Iwai T, Kawakami Y. Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin Cell Wall Skeleton Stimulation. Clin Cancer Res. 2006;12:7465–75.

    Article  CAS  PubMed  Google Scholar 

  53. Kawakami Y, Yaguchi T, Sumimoto H, Kudo-Saito C, Iwata-Kajihara T, Nakamura S, Tsujikawa T, Park JH, Popivanova BK, Miyazaki J, Kawamura N. Improvement of cancer immunotherapy by combining molecular targeted therapy. Front Oncol. 2013;3:136.

    Google Scholar 

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Acknowledgements

This studies were supported by Grants-in-Aid for Scientific Research (23240128, 26221005) from the Japan Society for Promotion of Science, a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in-Aid for Cancer Research (23-A-22, 19-14) from the Ministry of Health, Labour, and Welfare, Japan. We also thank technical support and editorial assistance of Ms. Misako Sakamoto and Ms. Ryoko Suzuki.

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Authors and Affiliations

  1. Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan

    Yutaka Kawakami, Li Qian, Naoshi Kawamura, Junichiro Miyazaki, Kinya Tsubota, Tomonari Kinoshita, Kenta Nakamura, Gaku Ohmura, Ryosuke Satomi, Juri Sugiyama, Hiroshi Nishio, Taeko Hayakawa, Boryana Popivanova, Sunthamala Nuchsupha, Tracy Hsin-ju Liu, Hajime Kamijuku, Chie Kudo-Saito, Nobuo Tsukamoto, Toshiharu Sakurai, Tomonobu Fujita & Tomonori Yaguchi

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  1. Yutaka Kawakami
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Correspondence to Yutaka Kawakami .

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Editors and Affiliations

  1. Department of Microbiology, Immunology a, University of California at Los Angeles,, Los Angeles, California, USA

    Benjamin Bonavida

  2. Institut Gustave Roussy, Villejuif, France

    Salem Chouaib

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Kawakami, Y. et al. (2015). Cancer Induced Immunosuppression and Its Modulation by Signal Inhibitors. In: Bonavida, B., Chouaib, S. (eds) Resistance of Cancer Cells to CTL-Mediated Immunotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-17807-3_13

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