The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

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

Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells
Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells
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.
Sugiyarto, Gessa
571d4680-798b-45e1-9e8b-9990f6ec53bd
Prossor, David
217071c7-149e-47dd-bea0-ab6924100cb3
Arcia Anaya, Eliuth David
ef9e7dfa-1fbc-4580-afba-9f5538bc2663
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Sugiyarto, Gessa
571d4680-798b-45e1-9e8b-9990f6ec53bd
Prossor, David
217071c7-149e-47dd-bea0-ab6924100cb3
Arcia Anaya, Eliuth David
ef9e7dfa-1fbc-4580-afba-9f5538bc2663
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4

Sugiyarto, Gessa, Prossor, David, Arcia Anaya, Eliuth David, Elliott, Timothy and James, Edward (2020) Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells. Immunotherapy Advances. (doi:10.1093/immadv/ltaa001).

Record type: Article

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.

This record has no associated files available for download.

More information

Accepted/In Press date: 19 October 2020
e-pub ahead of print date: 25 November 2020

Identifiers

Local EPrints ID: 445572
URI: http://eprints.soton.ac.uk/id/eprint/445572
PURE UUID: 65d38db6-5409-4c0d-82af-c1f0b4c42a97
ORCID for Gessa Sugiyarto: ORCID iD orcid.org/0000-0002-2686-0127
ORCID for Timothy Elliott: ORCID iD orcid.org/0000-0003-1097-0222
ORCID for Edward James: ORCID iD orcid.org/0000-0001-8638-7928

Catalogue record

Date deposited: 16 Dec 2020 17:31
Last modified: 22 Oct 2021 01:46

Export record

Altmetrics

Contributors

Author: Gessa Sugiyarto ORCID iD
Author: David Prossor
Author: Eliuth David Arcia Anaya
Author: Timothy Elliott ORCID iD
Author: Edward James ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×