Dataset Information

STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis.

ABSTRACT: One of the obstacles for cancer immunotherapy is the inefficiency of CD8(+) T-cell recruitment to tumors. STAT3 has been shown to suppress CD8(+) T-cell antitumor functions in various cancer models, in part by restricting accumulation of CD8(+) T cells. However, the underlying molecular mechanism by which STAT3 in CD8(+) T cells inhibits their accumulation in tumors remains to be defined. Here, we show that STAT3 signaling in CD8(+) T cells inhibits chemokine CXCL10 production by tumor-associated myeloid cells by reducing IFN? expression by T cells. We further demonstrate that ablating STAT3 in T cells allows expression of CXCR3, the receptor of CXCL10, on CD8(+) T cells, resulting in efficient accumulation of CD8(+) T cells at tumor sites. Blocking IFN? or CXCR3 impairs the accumulation of STAT3-deficient CD8(+) T cells in tumor and their antitumor effects. Together, our study reveals a negative regulation by STAT3 signaling in T cells on cross-talk between myeloid cells and T cells through IFN?/CXCR3/CXCL10, which is important for CD8(+) T cells homing to tumors. Our results thus provide new insights applicable to cancer immunotherapy and adoptive T-cell strategies.

SUBMITTER: Yue C

PROVIDER: S-EPMC4527884 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis.

Yue Chanyu C Shen Shudan S Deng Jiehui J Priceman Saul J SJ Li Wenzhao W Huang Austin A Yu Hua H

Cancer immunology research 20150529 8

One of the obstacles for cancer immunotherapy is the inefficiency of CD8(+) T-cell recruitment to tumors. STAT3 has been shown to suppress CD8(+) T-cell antitumor functions in various cancer models, in part by restricting accumulation of CD8(+) T cells. However, the underlying molecular mechanism by which STAT3 in CD8(+) T cells inhibits their accumulation in tumors remains to be defined. Here, we show that STAT3 signaling in CD8(+) T cells inhibits chemokine CXCL10 production by tumor-associate ...[more]

PMID: 26025380

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Dataset Information

STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis.

Publications

STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis.

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