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Cutting Edge: Recruitment, Retention, and Migration Underpin Functional Phenotypic Heterogeneity of Regulatory T Cells in Tumors

Abstract

Tumor-infiltrating regulatory T cells (Tregs) have been extensively studied as therapeutic targets. However, not all infiltrating T cells exert their functions equally, presumably because of their heterogeneity and substantial turnover in tissues. In this study, we hypothesized that intertissue migration underlies the functional heterogeneity of Tregs. To test this, we applied in vivo photolabeling to examine single-cell diversity of immunosuppressive molecules in mouse Tregs migrating to, remaining in, and emigrating from MC38 tumors. Neuropilin-1 (Nrp1) expression was inversely correlated with that of six other molecules associated with Treg function. Unsupervised clustering analyses revealed that clusters containing Tregs that were retained in tumors expressed high levels of the six functional molecules but not of Nrp1. However, these clusters represented only half of the Tregs migrating to the tumor, suggesting evolving heterogeneity of tumor-infiltrating Tregs. Thus, we propose progressive pathways of Treg activation and migration between tumors and draining lymph nodes.

Type Journal
ISBN 1550-6606 (Electronic) 0022-1767 (Linking)
Authors Ikebuchi, R.; Moriya, T.; Ueda, M.; Yasuda, I.; Kusumoto, Y.; Chtanova, T.; Tomura, M.
Responsible Garvan Author Dr Tatyana Chtanova
Publisher Name JOURNAL OF IMMUNOLOGY
Published Date 2021-08-31
Published Volume 207
Published Issue 3
Published Pages 771-776
Status Published in-print
DOI 10.4049/jimmunol.2001083
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/34290103