Resistance to immune checkpoint therapies by tumour-induced T-cell desertification and exclusion: key mechanisms, prognostication and new therapeutic opportunities

Br J Cancer. 2023 Oct;129(8):1212-1224. doi: 10.1038/s41416-023-02361-4. Epub 2023 Jul 15.


Immune checkpoint therapies (ICT) can reinvigorate the effector functions of anti-tumour T cells, improving cancer patient outcomes. Anti-tumour T cells are initially formed during their first contact (priming) with tumour antigens by antigen-presenting cells (APCs). Unfortunately, many patients are refractory to ICT because their tumours are considered to be 'cold' tumours-i.e., they do not allow the generation of T cells (so-called 'desert' tumours) or the infiltration of existing anti-tumour T cells (T-cell-excluded tumours). Desert tumours disturb antigen processing and priming of T cells by targeting APCs with suppressive tumour factors derived from their genetic instabilities. In contrast, T-cell-excluded tumours are characterised by blocking effective anti-tumour T lymphocytes infiltrating cancer masses by obstacles, such as fibrosis and tumour-cell-induced immunosuppression. This review delves into critical mechanisms by which cancer cells induce T-cell 'desertification' and 'exclusion' in ICT refractory tumours. Filling the gaps in our knowledge regarding these pro-tumoral mechanisms will aid researchers in developing novel class immunotherapies that aim at restoring T-cell generation with more efficient priming by APCs and leukocyte tumour trafficking. Such developments are expected to unleash the clinical benefit of ICT in refractory patients.

Publication types

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

MeSH terms

  • Antigens, Neoplasm
  • Conservation of Natural Resources
  • Humans
  • Immunotherapy
  • Neoplasms* / therapy
  • T-Lymphocytes*


  • Antigens, Neoplasm