Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response

Front Immunol. 2022 Feb 28:13:844866. doi: 10.3389/fimmu.2022.844866. eCollection 2022.

Abstract

Immunotherapy has become a key therapeutic strategy in the treatment of many cancers. As a result, research efforts have been aimed at understanding mechanisms of resistance to immunotherapy and how anti-tumor immune response can be therapeutically enhanced. It has been shown that tumor cell recognition by the immune system plays a key role in effective response to T cell targeting therapies in patients. One mechanism by which tumor cells can avoid immunosurveillance is through the downregulation of Major Histocompatibility Complex I (MHC-I). Downregulation of MHC-I has been described as a mechanism of intrinsic and acquired resistance to immunotherapy in patients with cancer. Depending on the mechanism, the downregulation of MHC-I can sometimes be therapeutically restored to aid in anti-tumor immunity. In this article, we will review current research in MHC-I downregulation and its impact on immunotherapy response in patients, as well as possible strategies for therapeutic upregulation of MHC-I.

Keywords: antigen presentation; cancer immunotherapy; immune checkpoint inhibition; immunoncology; major histocompatibility complex class-I.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Down-Regulation
  • Histocompatibility Antigens
  • Histocompatibility Antigens Class I*
  • Humans
  • Immunotherapy
  • Major Histocompatibility Complex
  • Neoplasms*

Substances

  • Histocompatibility Antigens
  • Histocompatibility Antigens Class I