STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis
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 IFNγ …
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 IFNγ …
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 IFNγ 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 IFNγ 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 IFNγ/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. Cancer Immunol Res; 3(8); 864–70. ©2015 AACR.
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