Cell biology

Immunosurveillance

Biology

Cancer research

Biochemistry

Immunology

Genetics

Myeloid

Immune system

In vitro

Cytotoxic T cell

Myeloid-derived Suppressor Cell

Suppressor

Cancer

European Journal of Immunology

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.

CD8<sup>+</sup> T‐cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation

CD8+ T‐cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation

CD8⁺ T‐cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation