Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells

Sugiyarto, Gessa, Prossor, David, Arcia Anaya, Eliuth David, Elliott, Timothy and James, Edward (2021) Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells. Immunotherapy Advances. (doi:10.1093/immadv/ltaa001).

Abstract

Regulatory T cells (Treg) play a major role in the suppression of protective anti-tumour T cell responses. In the CT26 BALB/c murine model of colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ T epitopes, AH1 and GSW11, which results in an absence of detectable IFN-γ producing GSW11-specific T cells in the spleen and lymph nodes of tumour challenged mice. Activation of GSW11-specific T cells correlates with protection against tumour progression. Here we show that GSW11-specific T cells are in fact induced in Treg-replete, CT26-bearing mice, where they make up the majority of tumour infiltrating CD8+ lymphocytes, but exhibit an ‘exhausted’ phenotype. This dysfunctional phenotype is induced early in the anti-tumour response in tumours. Depletion of Tregs prior to tumour challenge correlates with an altered T cell receptor (TcR) repertoire. Moreover, the avidity of GSW11-specific TcRs that expanded in the absence of Tregs was significantly lower compared to TcRs of CD8+populations that were diminished in protective anti-tumour responses. This indicates that Tregs suppress the induction of protective anti-tumour T cell responses and may signify that low avidity T cells play an important role in this protection.

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Contributors

Author: Gessa Sugiyarto

Author: Timothy Elliott

Author: Edward James

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