Chemotherapeutic and targeted agents can modulate the tumor microenvironment and increase the efficacy of immune checkpoint blockades

Mol Cancer. 2021 Feb 4;20(1):27. doi: 10.1186/s12943-021-01317-7.

Abstract

The development of immune checkpoint blockade (ICB)-based immunotherapy has dramatically changed methods of cancer treatment. This approach triggers a durable treatment response and prolongs patients' survival; however, not all patients can benefit. Accumulating evidence demonstrated that the efficacy of ICB is dependent on a robust antitumor immune response that is usually damaged in most tumors. Conventional chemotherapy and targeted therapy promote the antitumor immune response by increasing the immunogenicity of tumor cells, improving CD8+ T cell infiltration, or inhibiting immunosuppressive cells in the tumor microenvironment. Such immunomodulation provides a convincing rationale for the combination therapy of chemotherapeutics and ICBs, and both preclinical and clinical investigations have shown encouraging results. However, the optimal drug combinations, doses, timing, and sequence of administration, all of which affect the immunomodulatory effect of chemotherapeutics, as well as the benefit of combination therapy, are not yet determined. Future studies should focus on these issues and help to develop the optimal combination regimen for each cancer.

Keywords: antitumor immune response; chemotherapy; combination therapy; immune checkpoint blockade; targeted therapy; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Clinical Decision-Making
  • Disease Management
  • Disease Susceptibility
  • Drug Synergism
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunomodulation / drug effects
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Molecular Targeted Therapy* / methods
  • Neoplasms / drug therapy
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Tumor Microenvironment / drug effects*

Substances

  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors