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- Title
CD8<sup>+</sup> T-cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation.
- Authors
Zhang, Wang; Zhang, Chunyan; Li, Wenzhao; Deng, Jiehui; Herrmann, Andreas; Priceman, Saul J.; Liang, Wei; Shen, Shudan; Pal, Sumanta K.; Hoon, Dave S.B.; Yu, Hua
- Abstract
Increasing evidence suggests that premetastatic niches, consisting mainly of myeloid cells, provide microenvironment critical for cancer cell recruitment and survival to facilitate metastasis. While CD8+ T cells exert immunosurveillance in primary human tumors, whether they can exert similar effects on myeloid cells in the premetastatic environment is unknown. Here, we show that CD8+ T cells are capable of constraining premetastatic myeloid cell accumulation by inducing myeloid cell apoptosis in C57BL/6 mice. Ag-specific CD8+ T-cell cytotoxicity against myeloid cells in premetastatic lymph nodes is compromised by Stat3. We demonstrate here that Stat3 ablation in myeloid cells leads to CD8+ T-cell activation and increased levels of IFN-γ and granzyme B in the premetastatic environment. Furthermore, Stat3 negatively regulates soluble Ag cross-presentation by myeloid cells to CD8+ T cells in the premetastatic niche. Importantly, in tumor-free lymph nodes of melanoma patients, infiltration of activated CD8+ T cells inversely correlates with STAT3 activity, which is associated with a decrease in number of myeloid cells. Our study suggested a novel role for CD8+ T cells in constraining myeloid cell activity through direct killing in the premetastatic environment, and the therapeutic potential by targeting Stat3 in myeloid cells to improve CD8+ T-cell immunosurveillance against metastasis.
- Publication
European Journal of Immunology, 2015, Vol 45, Issue 1, p71
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201444467