Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related deaths among women worldwide.Previous studies have reported contradictory performance of chemokine CXC motif ligand 13(C...Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related deaths among women worldwide.Previous studies have reported contradictory performance of chemokine CXC motif ligand 13(CXCL13)in breast cancer.In this study,The Cancer Genome Atlas database analysis revealed that CXCL13 was overexpressed in various human cancers including breast carcinoma,and associated with good clinical prognosis in breast cancer.Flow cytometry detection also found upregulated intracellular CXCL13 expression in human breast cancer cell lines.To explore the possible role of CXCL13 in the breast cancer microenvironment,mouse triple negative breast cancer(TNBC)was lentivirally transfected to stably overexpress mouse CXCL13(4T1-CXCL13).Both parental 4T1 and 4T1-CXCL13 strains showed no in vitro or in vivo endogenous cell surface CXCR5 expression.In immune-competent BALB/c mice,the in vivo tumor growth of 4T1-CXCL13 was significantly inhibited and even completely eradicated,accompanied with increased infiltrations of CD4^(+),CD8^(+)T lymphocytes and CD11b^(+)CD11c^(+)DCs.Further investigations showed that CXCL13 expression in the 4T1 tumor microenvironment elicited long-term antitumor immune memory,and rejection of distal parental tumor.The antitumor activity of CXCL13 was remarkedly impaired in BALB/cA-nu nude mice,or in BALB/c mice with CD8^(+)T lymphocyte or NK cell depletion.Our investigation indicated that CXCL13 expression in TNBC triggered effective antitumor immunity by chemoattracting immune cell infiltrations and could be considered as a novel prognostic marker for TNBC.展开更多
滤泡辅助性T细胞(Tfh)是一种特殊类型的辅助性T细胞,位于生发中心的Tfh细胞表达CXCR5、Bcl-6、IL-21、CXCL13等分子,通过协助B细胞的分化在体液免疫应答过程中发挥关键作用。借助于流式细胞术、免疫组化等方法,发现Tfh细胞也存在于乳腺...滤泡辅助性T细胞(Tfh)是一种特殊类型的辅助性T细胞,位于生发中心的Tfh细胞表达CXCR5、Bcl-6、IL-21、CXCL13等分子,通过协助B细胞的分化在体液免疫应答过程中发挥关键作用。借助于流式细胞术、免疫组化等方法,发现Tfh细胞也存在于乳腺癌肿瘤组织中,其表型为PD-1 hi CXCR5 -ICOS int Bcl-6 int IL-21 +CXCL13 +,提示其参与了抗肿瘤免疫。Tfh细胞相关基因,特别是CXCL13基因的表达对乳腺癌预后判断有一定的价值。位于乳腺癌淋巴结中的Tfh细胞呈CXCR5 +Bcl-6 +Foxp3 -,可能接受其他CD4 + T细胞的调控或与其协同作用,影响体液免疫应答。目前对乳腺癌Tfh细胞的功能特征和预后价值尚缺乏系统和深入的研究,以乳腺癌Tfh细胞为靶点的进一步研究将有助于加深对乳腺癌肿瘤微环境的认识,同时也有可能为今后乳腺癌的免疫干预提供潜在的靶点。展开更多
基金Thisworkwas supported by theNationalNatural Science Foundation of China(grant No.81402354).
文摘Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related deaths among women worldwide.Previous studies have reported contradictory performance of chemokine CXC motif ligand 13(CXCL13)in breast cancer.In this study,The Cancer Genome Atlas database analysis revealed that CXCL13 was overexpressed in various human cancers including breast carcinoma,and associated with good clinical prognosis in breast cancer.Flow cytometry detection also found upregulated intracellular CXCL13 expression in human breast cancer cell lines.To explore the possible role of CXCL13 in the breast cancer microenvironment,mouse triple negative breast cancer(TNBC)was lentivirally transfected to stably overexpress mouse CXCL13(4T1-CXCL13).Both parental 4T1 and 4T1-CXCL13 strains showed no in vitro or in vivo endogenous cell surface CXCR5 expression.In immune-competent BALB/c mice,the in vivo tumor growth of 4T1-CXCL13 was significantly inhibited and even completely eradicated,accompanied with increased infiltrations of CD4^(+),CD8^(+)T lymphocytes and CD11b^(+)CD11c^(+)DCs.Further investigations showed that CXCL13 expression in the 4T1 tumor microenvironment elicited long-term antitumor immune memory,and rejection of distal parental tumor.The antitumor activity of CXCL13 was remarkedly impaired in BALB/cA-nu nude mice,or in BALB/c mice with CD8^(+)T lymphocyte or NK cell depletion.Our investigation indicated that CXCL13 expression in TNBC triggered effective antitumor immunity by chemoattracting immune cell infiltrations and could be considered as a novel prognostic marker for TNBC.
文摘滤泡辅助性T细胞(Tfh)是一种特殊类型的辅助性T细胞,位于生发中心的Tfh细胞表达CXCR5、Bcl-6、IL-21、CXCL13等分子,通过协助B细胞的分化在体液免疫应答过程中发挥关键作用。借助于流式细胞术、免疫组化等方法,发现Tfh细胞也存在于乳腺癌肿瘤组织中,其表型为PD-1 hi CXCR5 -ICOS int Bcl-6 int IL-21 +CXCL13 +,提示其参与了抗肿瘤免疫。Tfh细胞相关基因,特别是CXCL13基因的表达对乳腺癌预后判断有一定的价值。位于乳腺癌淋巴结中的Tfh细胞呈CXCR5 +Bcl-6 +Foxp3 -,可能接受其他CD4 + T细胞的调控或与其协同作用,影响体液免疫应答。目前对乳腺癌Tfh细胞的功能特征和预后价值尚缺乏系统和深入的研究,以乳腺癌Tfh细胞为靶点的进一步研究将有助于加深对乳腺癌肿瘤微环境的认识,同时也有可能为今后乳腺癌的免疫干预提供潜在的靶点。
