Mechanism and strategies of immunotherapy resistance in colorectal cancer

Front Immunol. 2022 Sep 27:13:1016646. doi: 10.3389/fimmu.2022.1016646. eCollection 2022.

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world. Although there are standard treatment options for CRC, most patients respond poorly to these treatments. Immunotherapies have gradually emerged due to the increasing awareness and understanding of tumor immunity, exhibiting good therapeutic efficacy in various cancers. Immunotherapies include cytokines, immune checkpoint inhibitors (ICIs), and adoptive cell therapies. In particular, ICIs, which are antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), or its ligand PD-L1, have been successfully applied clinically for solid tumors, relieving the inhibitory effect of the tumor microenvironment on T cells. However, only a minority of patients with cancer achieve a durable clinical response during immunotherapy. Several factors restrict the efficacy of immunotherapy, leading to the development of drug resistance. In this review, we aimed to discuss the current status of immunotherapy for CRC and elaborate on the mechanisms that mediate resistance to immunotherapy and other potential therapeutic strategies.

Keywords: colorectal cancer; drug resistance; immune checkpoint inhibitors; immunotherapy; potential therapeutic strategies.

Publication types

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

MeSH terms

  • B7-H1 Antigen*
  • CTLA-4 Antigen
  • Colorectal Neoplasms* / therapy
  • Cytokines
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunologic Factors
  • Immunotherapy
  • Ligands
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Cytokines
  • Immune Checkpoint Inhibitors
  • Immunologic Factors
  • Ligands
  • Programmed Cell Death 1 Receptor