目的:探讨三阴性乳腺癌(three yin breast cancer,TNBC)中pSTAT1和PD-L1的表达及其相关性研究。方法:对50例三阴性乳腺癌(TNBC)、70例非三阴性乳腺癌(non three yin breast cancer,non-TNBC)以及36例乳腺良性病变(腺病)组织,采用免疫组...目的:探讨三阴性乳腺癌(three yin breast cancer,TNBC)中pSTAT1和PD-L1的表达及其相关性研究。方法:对50例三阴性乳腺癌(TNBC)、70例非三阴性乳腺癌(non three yin breast cancer,non-TNBC)以及36例乳腺良性病变(腺病)组织,采用免疫组织化学法观察pSTAT1和PD-L1的表达情况,并分析其相关性;使用STAT1激活剂2-NP诱导MDA-MB-468和MCF-7,通过qRT-PCR比较PD-L1、IRF-1在处理组与对照组间的相对表达量。结果:(1)TNBC中pSTAT1和PD-L1均高表达,与non-TNBC差异具有统计学意义(P<0.05),在乳腺腺病中pSTAT1和PD-L1均不表达;(2)观察发现,TNBC中pSTAT1与PD-L1可能存在共表达,通过统计学分析pSTAT1与PD-L1表达具有相关性(P<0.05);(3)pSTAT1在TNBC具有四种表达模式;(4)2-NP作用后,MDA-MB-468和MCF-7中PD-L1相对表达均增高(P<0.05),但IRF-1仅在MDA-MB-468中表达量增高(P<0.05),与MCF-7相比MDA-MB-468中IRF-1、PD-L的表达量变化显著。结论:p STAT1和PD-L1在TNBC中高表达,PD-L1的高表达可能与TNBC中STAT1-IRF1-PDL1通路上调有关,pSTAT1有望成为TNBC治疗的重要靶标。展开更多
Signal transducer and activator of transcription （STAT） proteins play an important role in cytokine signaling pathways and regulation of immune responses. The balance of the phosphorylated （activated） STAT1 （pST...Signal transducer and activator of transcription （STAT） proteins play an important role in cytokine signaling pathways and regulation of immune responses. The balance of the phosphorylated （activated） STAT1 （pSTAT1） and STAT3 （pSTAT3） has been documented in cancer immunology. In this study, we investigated the dynamic balance of pSTAT1 and pSTAT3 in C57BL/6 mice infected with either a nonlethal （Py17XNL） or lethal （Py17XL） strain of Plasmodium yoelii. Both Py17XNL and Py17XL infections induced a maximum activation of STAT1 and STAT3 on the first day after parasite inoculation. Additionally, the Py17XNL infection induced a pSTAT1- dominant response in mice during the early stage of infection, with the resolution of parasitemia. In contrast, Py17XL infection induced a pSTAT3-dominant response during the early phase of infection, with the death of the animals. Our results indicated that maximum activation of STAT1 and STAT3 occurred much earlier than the peak levels of cytokines induced by Plasmodium yoelii infection based on previous reports and that infection with Py17XNL and Py17XL induced different dynamic patterns of pSTAT1 and pSTAT3 balance.展开更多
文摘目的:探讨三阴性乳腺癌(three yin breast cancer,TNBC)中pSTAT1和PD-L1的表达及其相关性研究。方法:对50例三阴性乳腺癌(TNBC)、70例非三阴性乳腺癌(non three yin breast cancer,non-TNBC)以及36例乳腺良性病变(腺病)组织,采用免疫组织化学法观察pSTAT1和PD-L1的表达情况,并分析其相关性;使用STAT1激活剂2-NP诱导MDA-MB-468和MCF-7,通过qRT-PCR比较PD-L1、IRF-1在处理组与对照组间的相对表达量。结果:(1)TNBC中pSTAT1和PD-L1均高表达,与non-TNBC差异具有统计学意义(P<0.05),在乳腺腺病中pSTAT1和PD-L1均不表达;(2)观察发现,TNBC中pSTAT1与PD-L1可能存在共表达,通过统计学分析pSTAT1与PD-L1表达具有相关性(P<0.05);(3)pSTAT1在TNBC具有四种表达模式;(4)2-NP作用后,MDA-MB-468和MCF-7中PD-L1相对表达均增高(P<0.05),但IRF-1仅在MDA-MB-468中表达量增高(P<0.05),与MCF-7相比MDA-MB-468中IRF-1、PD-L的表达量变化显著。结论:p STAT1和PD-L1在TNBC中高表达,PD-L1的高表达可能与TNBC中STAT1-IRF1-PDL1通路上调有关,pSTAT1有望成为TNBC治疗的重要靶标。
基金for providing the Py17XNL strain and the Malaria Research and Reference Reagent Resource Center (MR4, MAL88851-01265293) for donating the Py17XL strain of Plasmodium yoelii.
文摘Signal transducer and activator of transcription （STAT） proteins play an important role in cytokine signaling pathways and regulation of immune responses. The balance of the phosphorylated （activated） STAT1 （pSTAT1） and STAT3 （pSTAT3） has been documented in cancer immunology. In this study, we investigated the dynamic balance of pSTAT1 and pSTAT3 in C57BL/6 mice infected with either a nonlethal （Py17XNL） or lethal （Py17XL） strain of Plasmodium yoelii. Both Py17XNL and Py17XL infections induced a maximum activation of STAT1 and STAT3 on the first day after parasite inoculation. Additionally, the Py17XNL infection induced a pSTAT1- dominant response in mice during the early stage of infection, with the resolution of parasitemia. In contrast, Py17XL infection induced a pSTAT3-dominant response during the early phase of infection, with the death of the animals. Our results indicated that maximum activation of STAT1 and STAT3 occurred much earlier than the peak levels of cytokines induced by Plasmodium yoelii infection based on previous reports and that infection with Py17XNL and Py17XL induced different dynamic patterns of pSTAT1 and pSTAT3 balance.
