Tackling Resistance to Cancer Immunotherapy: What Do We Know?

Molecules. 2020 Sep 8;25(18):4096. doi: 10.3390/molecules25184096.

Abstract

Cancer treatment has evolved tremendously in the last few decades. Immunotherapy has been considered to be the forth pillar in cancer treatment in addition to conventional surgery, radiotherapy, and chemotherapy. Though immunotherapy has resulted in impressive response, it is generally limited to a small subset of patients. Understanding the mechanisms of resistance toward cancer immunotherapy may shed new light to counter that resistance. In this review, we highlighted and summarized two major hurdles (recognition and attack) of cancer elimination by the immune system. The mechanisms of failure of some available immunotherapy strategies were also described. Moreover, the significance role of immune compartment for various established cancer treatments were also elucidated in this review. Then, the mechanisms of combinatorial treatment of various conventional cancer treatment with immunotherapy were discussed. Finally, a strategy to improve immune cancer killing by characterizing cancer immune landscape, then devising treatment based on that cancer immune landscape was put forward.

Keywords: T cell; antigen presentation; cancer; immune checkpoint; immune escape; immunosuppression; immunotherapy; resistance; treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology
  • Chemotaxis, Leukocyte / genetics
  • Chemotaxis, Leukocyte / immunology
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm* / genetics
  • Drug Resistance, Neoplasm* / immunology
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / adverse effects
  • Immunotherapy* / methods
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome
  • Tumor Escape / drug effects
  • Tumor Escape / genetics
  • Tumor Escape / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Antigens, Neoplasm
  • HLA Antigens
  • Immune Checkpoint Inhibitors