Convergent inducers and effectors of T cell paralysis in the tumour microenvironment.
Details
Serval ID
serval:BIB_9742FEA16017
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Convergent inducers and effectors of T cell paralysis in the tumour microenvironment.
Journal
Nature reviews. Cancer
ISSN
1474-1768 (Electronic)
ISSN-L
1474-175X
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: aheadofprint
Publication Status: aheadofprint
Abstract
Tumorigenesis embodies the formation of a heterotypic tumour microenvironment (TME) that, among its many functions, enables the evasion of T cell-mediated immune responses. Remarkably, most TME cell types, including cancer cells, fibroblasts, myeloid cells, vascular endothelial cells and pericytes, can be stimulated to deploy immunoregulatory programmes. These programmes involve regulatory inducers (signals-in) and functional effectors (signals-out) that impair CD8 <sup>+</sup> and CD4 <sup>+</sup> T cell activity through cytokines, growth factors, immune checkpoints and metabolites. Some signals target specific cell types, whereas others, such as transforming growth factor-β (TGFβ) and prostaglandin E <sub>2</sub> (PGE <sub>2</sub> ), exert broad, pleiotropic effects; as signals-in, they trigger immunosuppressive programmes in most TME cell types, and as signals-out, they directly inhibit T cells and also modulate other cells to reinforce immunosuppression. This functional diversity and redundancy pose a challenge for therapeutic targeting of the immune-evasive TME. Fundamentally, the commonality of regulatory programmes aimed at abrogating T cell activity, along with paracrine signalling between cells of the TME, suggests that many normal cell types are hard-wired with latent functions that can be triggered to prevent inappropriate immune attack. This intrinsic capability is evidently co-opted throughout the TME, enabling tumours to evade immune destruction.
Pubmed
Create date
01/11/2024 15:44
Last modification date
02/11/2024 7:10