Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer
Song, ErweiNote: Order does not necessarily reflect citation order of authors.
MetadataShow full item record
CitationSu, 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.
AbstractThe 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32630628