Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

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Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

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Title: Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer
Author: Su, Shicheng; Liao, Jianyou; Liu, Jiang; Huang, Di; He, Chonghua; Chen, Fei; Yang, LinBing; Wu, Wei; Chen, Jianing; Lin, Ling; Zeng, Yunjie; Ouyang, Nengtai; Cui, Xiuying; Yao, Herui; Su, Fengxi; Huang, Jian-dong; Lieberman, Judy; Liu, Qiang; Song, Erwei

Note: Order does not necessarily reflect citation order of authors.

Citation: Su, S., J. Liao, J. Liu, D. Huang, C. He, F. Chen, L. Yang, et al. 2017. “Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer.” Cell Research 27 (4): 461-482. doi:10.1038/cr.2017.34. http://dx.doi.org/10.1038/cr.2017.34.
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Abstract: The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4+ T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCL18-producing macrophages. Moreover, adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner. In human breast cancer xenografts in humanized mice, blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3, a CCL18 receptor, significantly reduces intratumoral Tregs and inhibits tumor progression. These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ. Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy.
Published Version: doi:10.1038/cr.2017.34
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385617/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630628
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