Abstract 3959: CCL18-recruited naïve CD4+T cells are converted to tumor-infiltrating regulatory T cells in breast cancer and suppress antitumor immunity
Cancer Research(2017)
Abstract
Tumor-infiltrating regulatory T cells (Tregs) play a central role in tumor immunosuppression. However, it remains unclear whether they are directly recruited from peripheral blood or converted from infiltrating naive T cells. Here, full-length TCR α/β repertoire analysis of different T cell subsets from peripheral blood, primary tumors and draining lymph nodes in patents suggests that Tregs in human breast cancer are mainly converted from tumor-infiltrating naive CD4+ T cells. Infiltration of naive CD4+ T cells and Tregs are closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells in the tumors are recruited by tumor-associated macrophages (TAMs) via CCL18. In addition, naive T cells and memory T cells exhibit distinctive chemotactic response due to different expression of regulator of G-protein signaling 1(RGS1). Specific silencing CCL18 receptor-PITPNM3 in naive CD4+ T cells using CD4 aptamer-siRNA blocks their chemotaxis, and thus reduces infiltrating Tregs and inhibits tumor progression in humanized mice. By comparison, silencing RGS1 in memory CD8+ T cells using CD8 aptamer-siRNA enhance their recruitment to tumors and anti-tumor immune response in vivo. These findings provide mechanistic insights for Treg enrichment in breast cancer and suggest that modification of the CCL18-PITPNM3-RGS1 signaling pathway may be an attractive strategy for anticancer immunotherapy. Note: This abstract was not presented at the meeting. Citation Format: Shicheng Su, Jianyou Liao, Jiang Liu, Qiang Liu, Erwei Song. CCL18-recruited naive CD4+ T cells are converted to tumor-infiltrating regulatory T cells in breast cancer and suppress antitumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3959. doi:10.1158/1538-7445.AM2017-3959
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Key words
breast cancer,cells,tumor-infiltrating
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