CD8+ T‐cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation. Issue 1 (10th November 2014)

• Record Type: Journal Article
• 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
• Is Part Of: European journal of immunology. Volume 45:Issue 1(2015)
• Page Start: 71
• Page End: 81
• Publication Date: 2014-11-10
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201444467
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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<sup>+</sup> 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<sup>+</sup> T cells are capable of constraining premetastatic myeloid cell accumulation by inducing myeloid cell apoptosis in C57BL/6 mice. Ag‐specific CD8<sup>+</sup> T‐cell cytotoxicity against myeloid cells in premetastatic lymph nodes is compromised by Stat3. We demonstrate here that <italic>Stat3</italic> ablation in myeloid cells leads to CD8<sup>+</sup> 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<sup>+</sup> T cells in the premetastatic niche. Importantly, in tumor‐free lymph nodes of melanoma patients, infiltration of activated CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T‐cell immunosurveillance against metastasis.</p> </abstract>