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Altered chemokine production and accumulation of regulatory T cells in intestinal adenomas of APC(Min/+) mice.

Journal article
Authors Paulina Akeus
Veronica Langenes
Astrid von Mentzer
Ulf Yrlid
Åsa Sjöling
Pushpa Saksena
Sukanya Raghavan
Marianne Quiding-Järbrink
Published in Cancer immunology, immunotherapy : CII
Volume 63
Issue 8
Pages 807-19
ISSN 1432-0851
Publication year 2014
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 807-19
Language en
Links dx.doi.org/10.1007/s00262-014-1555-...
Keywords Adenocarcinoma, immunology, Adenoma, immunology, Aged, Animals, Chemokines, biosynthesis, immunology, Colorectal Neoplasms, immunology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, T-Lymphocytes, Regulatory, immunology
Subject categories Basic Medicine, Tumour immunology

Abstract

Tumor progression in the colon moves from aberrant crypt foci to adenomatous polyps to invasive carcinomas. The composition of the tumor-infiltrating leukocyte population affects the ability of the immune system to fight the tumor. T cell infiltration into colorectal adenocarcinomas, particularly T helper 1 (Th1) type T cells as well as increased regulatory T cell (Treg) frequencies, is correlated with improved prognosis. However, whether Th1 cells and Tregs are already present at the adenoma stage is not known. In this study, the APC(Min/+) mouse model of intestinal adenomatous polyposis was used to investigate tumor-associated lymphocyte subsets and the mechanisms of their accumulation into gastrointestinal adenomas. Compared to unaffected tissue, adenomas accumulated CD4(+)FoxP3(+) putative Treg in parallel with lower frequencies of conventional T cells and B cells. The accumulation of Treg was also observed in human adenomatous polyps. Despite high Treg numbers, the function of conventional T cells present in the APC(Min/+) adenomas was not different from those in the unaffected tissue. Adenomas displayed an altered chemokine balance, with higher CCL17 and lower CXCL11 and CCL25 expression than in the unaffected tissue. In parallel, CXCR3(+) Tregs were largely absent from adenomas. The data indicate that already in early stages of tumor development, the balance of lymphocyte-recruiting chemokines is altered possibly contributing to the observed shift toward higher frequencies of Treg.

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