Signal transducers and activators of transcription 5(Stat5)is known to engage in regulating the differentiation and effector function of various subsets of T helper cells.However,how Stat5 regulates the antitumor acti...Signal transducers and activators of transcription 5(Stat5)is known to engage in regulating the differentiation and effector function of various subsets of T helper cells.However,how Stat5 regulates the antitumor activity of tumor-infiltrating CD4^(+)T cells is largely unknown.Here,we showed that mice with specific deletion of Stat5 in CD4^(+)T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4^(+)tumor-infiltrating lymphocytes(TILs)remolding.Especially,we confirmed that Stat5-deficient CD4^(+)naïve T cells were prone to polarization of two subtypes of Th17 cells:IFN-γ^(+)and IFN-γ^(-)Th17 cells,which exhibited increased anti-melanoma activity through enhanced activation of Notch1 pathway compared with wild type Th17 cells.Our study therefore revealed a novel function of Stat5 in regulating tumor-specific Th17 cell differentiation and function in melanoma.This study also provided a new possibility for targeting Stat5 and other Th17-associated pathways to develop novel immunotherapies for melanoma patients.展开更多
基金supported by start-up funds for Prof. Xin-Yuan Fu (139170082)sponsored by West China Hospital, Sichuan Universityin part by the Chinese National Natural Science Funds (81902947)。
文摘Signal transducers and activators of transcription 5(Stat5)is known to engage in regulating the differentiation and effector function of various subsets of T helper cells.However,how Stat5 regulates the antitumor activity of tumor-infiltrating CD4^(+)T cells is largely unknown.Here,we showed that mice with specific deletion of Stat5 in CD4^(+)T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4^(+)tumor-infiltrating lymphocytes(TILs)remolding.Especially,we confirmed that Stat5-deficient CD4^(+)naïve T cells were prone to polarization of two subtypes of Th17 cells:IFN-γ^(+)and IFN-γ^(-)Th17 cells,which exhibited increased anti-melanoma activity through enhanced activation of Notch1 pathway compared with wild type Th17 cells.Our study therefore revealed a novel function of Stat5 in regulating tumor-specific Th17 cell differentiation and function in melanoma.This study also provided a new possibility for targeting Stat5 and other Th17-associated pathways to develop novel immunotherapies for melanoma patients.
