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Cancer-associated fibroblasts induce antigen-specific deletion of CD8 + T Cells to protect tumour cells.

Authors
  • Lakins, Matthew A
  • Ghorani, Ehsan
  • Munir, Hafsa
  • Martins, Carla P
  • Shields, Jacqueline Dianne
Publication Date
Mar 05, 2018
Source
Apollo - University of Cambridge Repository
Keywords
Language
English
License
Unknown
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Abstract

Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and “normal” stromal cells exists, may be critical for T cell suppression. We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+ T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralization of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Thus, CAFs support T cell suppression within the tumour microenvironment by a mechanism dependent on immune checkpoint activation.

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