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

Wang, Mona Meng, Coupland, Sarah E ORCID: 0000-0002-1464-2069, Aittokallio, Tero and Figueiredo, Carlos R (2023) Resistance to immune checkpoint therapies by tumour-induced T-cell desertification and exclusion: key mechanisms, prognostication and new therapeutic opportunities. BRITISH JOURNAL OF CANCER, 129 (8). pp. 1212-1224.

Access the full-text of this item by clicking on the Open Access link.

Official URL: http://dx.doi.org/10.1038/s41416-023-02361-4

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	T-Lymphocytes, Humans, Neoplasms, Antigens, Neoplasm, Immunotherapy, Conservation of Natural Resources
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	28 Sep 2023 10:13
Last Modified:	27 Oct 2023 10:33
DOI:	10.1038/s41416-023-02361-4
Open Access URL:	https://doi.org/10.1038/s41416-023-02361-4
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3173153