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A distinct chemokine axis does not account for enrichment of Foxp3 + CD 4 + T cells in carcinogen‐induced fibrosarcomas
Author(s) -
Ondondo Beatrice,
Colbeck Emily,
Jones Emma,
Smart Kathryn,
Lauder Sarah N.,
Hindley James,
Godkin Andrew,
Moser Bernhard,
Ager Ann,
Gallimore Awen
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12430
Subject(s) - ccl5 , cxcr3 , foxp3 , chemokine , biology , cancer research , cxcl10 , chemokine receptor , ccl17 , population , immunology , ccl22 , t cell , microbiology and biotechnology , inflammation , il 2 receptor , medicine , immune system , environmental health
Summary The frequency of CD 4 + Foxp3 + regulatory T (Treg) cells is often significantly increased in the blood of tumour‐bearing mice and people with cancer. Moreover, Treg cell frequencies are often higher in tumours compared with blood and lymphoid organs. We wished to determine whether certain chemokines expressed within the tumour mass selectively recruit Treg cells, 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 CD 4 + Foxp3 − and CD 4 + Foxp3 + T cells were compared. These analyses revealed that the tumours are characterized by expression of inflammatory chemokines ( CCL 2, CCL 5, CCL 7, CCL 8, CCL 12, CXCL 9, CXCL 10 and CX 3 CL 1), reflected by an enrichment of activated Foxp3 − and Foxp3 + T cells expressing T helper type 1‐associated chemokine receptors. Notably, we found that CXCR 3 + T cells were significantly enriched in the tumours although curiously we found no evidence that CXCR 3 was required for their recruitment. Instead, CXCR 3 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 characterized 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 cell accumulation in tumours.