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Melanoma pp 133-142 | Cite as

Immunobiology of the Melanoma Microenvironment

  • Yutaka Kawakami
  • Adam I. Riker
Chapter

Abstract

Melanoma has been a prototype cancer to investigate tumor immunity and development of immunotherapy. The recent analyses on the patients treated with immune checkpoint inhibitors made a great progress of human tumor immunology. However, the response rate of PD-1/PD-L1 Ab therapy is about 30% so that the identification of biomarkers to select appropriate patients and immunotherapies as well as the improvement of efficacy possibly through combination treatment are required. Pretreatment immune status is different among patients, and correlated with prognosis and response to cancer therapies including immunotherapy. It may be defined by cancer cell’s genetic characteristics, patients’ immune reactivity, and environmental factors. In the T-cell-inflamed melanoma, adaptive immune resistance such as PD-1/PD-L1 interaction prevents melanoma attack by T cells specific for tumor antigens such as DNA mutation-derived neo-antigens. Blocking such resistant mechanisms may reinvigorate T cells to eradicate melanoma cells. Partially exhausted T cells expressing PD-1 and CTLA4 appear to be expanded following PD-1/PD-L1 blockade and may contribute to their antitumor effects. In T-cell non-inflamed melanoma, primary immune resistance including cancer cell-derived immunosuppressive factors, loss of immune-inducing factors from cancer cells, mesenchymal tumor microenvironment, and other genetic alternations prevents induction and tumor infiltration of antitumor T cells even in the presence of immunogenic tumor antigens. Depletion of such negative factors may convert nonresponders to responders, indicating that combination immunotherapy may augment the efficacy of current immunotherapies. Further understanding of immunobiology using multi-omics and systematic immune analyses is required to identify better biomarkers and therapeutic targets for the next-generation immunotherapy for melanoma.

Keywords

Immunobiology Immunotherapy Immune checkpoint blockade PD-1/PD-L1 CTLA4 Neo-antigen T-cell inflamed Adaptive immune resistance Oncogene Immunosuppression 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Cellular Signaling, Institute for Advanced Medical ResearchKeio University School of MedicineTokyoJapan
  2. 2.Section of Surgical Oncology, Department of SurgeryLouisiana State University, School of Medicine, LSU Health-New OrleansNew OrleansUSA

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