Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors

Hindley, James Philip, Ferreira, Cristina, Jones, Emma, Lauder, Sarah Nicol, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Wynn, Katherine, Betts, Gareth James, Singh, Yogesh, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567, Dyson, Julian and Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 2011. Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors. Cancer Research 71 (3) , pp. 736-746. 10.1158/0008-5472.CAN-10-1797

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Abstract

A significant enrichment of CD4+Foxp3+ T cells (regulatory T cells, Treg) is frequently observed in murine and human carcinomas. As Tregs can limit effective antitumor immune responses, thereby promoting tumor progression, it is important that the mechanisms underpinning intratumoral accumulation of Tregs are identified. Because of evidence gathered mostly in vitro, the conversion of conventional T cells (Tconv) into Tregs has been proposed as one such mechanism. We assessed the contribution of conversion in vivo by analyzing the TCR (T-cell receptor) repertoires of Tconvs and Tregs in carcinogen-induced tumors in mice. Our results indicate that the TCR repertoires of Tregs and Tconvs within tumor-infiltrating lymphocytes (TIL) are largely distinct. Indeed, the cell population with the greatest degree of repertoire similarity with tumor-infiltrating Tregs was the Treg population from the tumor-draining lymph node. These findings demonstrate that conversion of Tconvs does not contribute significantly to the accumulation of tumor-infiltrating Tregs; rather, Tconvs and Tregs arise from different populations with unique TCR repertoires. Enrichment of Tregs within TILs most likely, therefore, reflects differences in the way that Tregs and Tconvs are influenced by the tumor microenvironment. Elucidating the nature of these influences may indicate how the balance between tumor-infiltrating Tregs and Tconvs can be manipulated for therapeutic purposes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	American Association for Cancer Research
ISSN:	0008-5472
Last Modified:	06 Nov 2022 14:36
URI:	https://orca.cardiff.ac.uk/id/eprint/29894

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