Small molecular drugs reshape tumor microenvironment to synergize with immunotherapy

Oncogene. 2021 Feb;40(5):885-898. doi: 10.1038/s41388-020-01575-7. Epub 2020 Dec 7.

Abstract

Recently, immune checkpoint blockade (ICB), especially anti-programmed death 1 (anti-PD-1) and anti-programmed death-ligand 1 (anti-PD-L1) therapy, has become an increasingly appealing therapeutic strategy for cancer patients. However, only a small portion of patients responds to anti-PD treatment. Therefore, treatment strategies are urgently needed to reverse the ICB-resistant tumor microenvironment (TME). It has become clear that the TME has diminished innate sensing that is critical to activate adaptive immunity. In addition, tumor cells upregulate various immunosuppressive factors to diminish the immune response and resist immunotherapy. In this review, we briefly update the current small molecular drugs that could synergize with immunotherapy, especially anti-PD therapy. We will discuss the modes of action by those drugs including inducing innate sensing and limiting immunosuppressive factors in the TME.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / immunology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunologic Factors / therapeutic use
  • Immunotherapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Signal Transduction / drug effects
  • Small Molecule Libraries / therapeutic use*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Immunologic Factors
  • Small Molecule Libraries