Overcome the tumor immunotherapy resistance by combination of the HDAC6 inhibitors with antitumor immunomodulatory agents

Bioorg Chem. 2021 Apr:109:104754. doi: 10.1016/j.bioorg.2021.104754. Epub 2021 Feb 20.

Abstract

Tumor immunotherapy is currently subject of intense scientific and clinical developments. In previous decade, therapists used natural immune system from the human body to treat several diseases. Although tumor immune disease is a big challenge, combinatorial therapeutic strategy has been succeeded to show the clinical significance. In this context, we discuss the HDAC6 and tumor immune diseases relationship. Also, we summarized the current state of knowledge that based on the combination treatments of the HDAC6 inhibitors (HDAC6is) with antitumor immunomodulatory agents. We observed that, the combination therapies slow down the tumor immune diseases by blocking the aggresome and proteasome pathway. The combination therapy was able to reduce M2 macrophage and increasing PD-L1 blockade sensitivity. Most importantly, multiple combinations of HDAC6is with other agents may consider as potential strategies to treat tumor immune diseases, by reducing the side effects and improve efficacy for the future clinical development.

Keywords: Antitumor immunomodulatory agent; Combination therapy; HDAC6 inhibitor; Tumor immune diseases.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Histone Deacetylase 6 / antagonists & inhibitors*
  • Histone Deacetylase 6 / chemistry
  • Histone Deacetylase 6 / immunology
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Immunotherapy*
  • Molecular Structure
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Immunologic Factors
  • HDAC6 protein, human
  • Histone Deacetylase 6