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Wiley, Immunology, 1(145), p. 94-104, 2015

DOI: 10.1111/imm.12430

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A distinct chemokine axis does not account for enrichment of Foxp3+ CD4+ T cells in carcinogen-induced fibrosarcomas

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The frequency of CD4+Foxp3+ regulatory T cells (Tregs) is often significantly increased in the blood of tumour-bearing mice and people with cancer. Moreover, Treg frequencies are often higher in tumours compared to blood and lymphoid organs. We wished to determine whether certain chemokines expressed within the tumour mass selectively recruit Tregs, thereby contributing to their enrichment within the tumour-infiltrating lymphocyte pool. To achieve this goal, the chemokine profile of carcinogen-induced fibrosarcomas was determined, and the chemokine receptor expression profiles of both CD4+Foxp3- and CD4+Foxp3+ T cells were compared. These analyses revealed that the tumours are characterised by expression of inflammatory chemokines (CCL2, CCL5, CCL7, CCL8, CCL12, CXCL9, CXCL10 and CX3CL1), reflected by an enrichment of activated Foxp3- and Foxp3+ T cells expressing Th1-associated chemokine receptors. Notably, we found that CXCR3+ T cells were significantly enriched in the tumours although curiously we found no evidence that CXCR3 was required for their recruitment. Instead, CXCR3 marks a population of activated Foxp3- and Foxp3+ T cells, which use multiple and overlapping ligand receptor pairs to guide their migration to tumours. Collectively, these data indicate that enrichment of Foxp3+ cells in tumours characterised by expression of inflammatory chemokines, does not occur via a distinct chemokine axis thus selective chemokine blockade is unlikely to represent a meaningful therapeutic strategy for preventing Treg accumulation in tumours.This article is protected by copyright. All rights reserved.