Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy

Cell Mol Immunol. 2023 Apr;20(4):318-340. doi: 10.1038/s41423-023-00980-8. Epub 2023 Feb 24.

Abstract

Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment. Despite demonstrable progress, most patients fail to respond or achieve durable responses due to primary or acquired ICB resistance. Recently, tumor epithelial-to-mesenchymal plasticity (EMP) was identified as a critical determinant in regulating immune escape and immunotherapy resistance in cancer. In this review, we summarize the emerging role of tumor EMP in ICB resistance and the tumor-intrinsic or extrinsic mechanisms by which tumors exploit EMP to achieve immunosuppression and immune escape. We discuss strategies to modulate tumor EMP to alleviate immune resistance and to enhance the efficiency of ICB therapy. Our discussion provides new prospects to enhance the ICB response for therapeutic gain in cancer patients.

Keywords: Epithelial-to-mesenchymal plasticity (EMP); immune checkpoint blockade (ICB); immunotherapy resistance; tumor microenvironment (TME).

Publication types

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

MeSH terms

  • Humans
  • Immunosuppression Therapy
  • Immunotherapy
  • Neoplasms* / pathology
  • Tumor Microenvironment