目的探讨三阴型乳腺癌(triple negative breast cancer,TNBC)间质肿瘤浸润淋巴细胞(stromal tumor-infiltrating lymphocytes,sTILs)程序性死亡配体-1(programmed death ligand-1,PD-L1)蛋白的表达及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs...目的探讨三阴型乳腺癌(triple negative breast cancer,TNBC)间质肿瘤浸润淋巴细胞(stromal tumor-infiltrating lymphocytes,sTILs)程序性死亡配体-1(programmed death ligand-1,PD-L1)蛋白的表达及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs亚群与临床病理特征的相关性及对患者预后的影响。方法收集遵义医科大学附属医院2015~2019年病理资料完善的女性TNBC标本92例,评估每张HE切片肿瘤区域内sTILs的浸润密度,采用免疫组化EnVision法检测92例TNBC中sTILs的PD-L1蛋白表达情况及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs的浸润密度。结果TNBC中sTILs与Ki-67指数(P=0.001)显著相关;CD4^(+)、CD8^(+)sTILs与肿瘤大小(P=0.012、0.006)和Ki-67指数(P=0.047、0.006)显著相关;Foxp3^(+)sTILs、PD-L1^(+)sTILs与组织学分级(P=0.001、0.005)显著相关。TNBC中sTILs与CD4^(+)、CD8^(+)sTILs呈正相关(P<0.05),与PD-L1^(+)sTILs存在显著相关性(P<0.05),与Foxp3^(+)sTILs无相关性。TNBC预后的单因素和多因素分析发现,PD-L1^(+)sTILs和淋巴结转移阳性患者具有更短的总生存期,而sTILs及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs与患者的预后无相关性。结论TNBC中sTILs及CD4^(+)、CD8^(+)sTILs浸润密度可能与乳腺癌肿瘤细胞增殖有关,Foxp3^(+)sTILs可能与乳腺癌肿瘤细胞分化程度有关,而PD-L1^(+)sTILs和淋巴结转移阳性可能与TNBC的不良预后相关。展开更多
目的对原发性肝癌(hepatocellu lar carc inom a,HCC)射频消融治疗(rad iofrequency ab lation,RFA)前后肿瘤内部及边缘热休克蛋白70(heat shock prote in,HSP70)的表达、CD8+T细胞数量的变化以及RFA治疗后,肿瘤边缘HSP70表达与肿瘤边缘...目的对原发性肝癌(hepatocellu lar carc inom a,HCC)射频消融治疗(rad iofrequency ab lation,RFA)前后肿瘤内部及边缘热休克蛋白70(heat shock prote in,HSP70)的表达、CD8+T细胞数量的变化以及RFA治疗后,肿瘤边缘HSP70表达与肿瘤边缘CD8+T细胞数量之间的关系进行观察,探讨RFA治疗对原发性肝癌局部免疫功能状态的影响及其可能的临床意义。方法对17例HCC分别在RFA治疗前、后1个月,于肿瘤内部和肿瘤边缘超声引导下穿刺活检取样;采用PowerV isionTM二步染色法进行免疫组化分析,测定HSP70的表达、CD8+T细胞的数量;随访HCC复发/新生情况。结果RFA治疗后肿瘤边缘组织HSP70表达增强(Z=3.337,P=0.001)、CD8+T细胞数量增多(Z=1.996,P=0.049);RFA治疗后,≤4 cm肿瘤组的占位边缘CD8+T细胞数量高于>4 cm肿瘤组(Z=1.966,P=0.048)。RFA治疗后,边缘组织HSP70表达与CD8+T细胞数量之间呈正相关关系(r=0.489,P=0.046);RFA治疗后,无复发或新生组的占位边缘组织HSP70表达和CD8+T细胞数量分别高于复发或新生组(Z=2.009,P=0.045;Z=2.007,P=0.045)。结论RFA治疗后边缘HSP70表达增强、CD8+T细胞数量增多,显示RFA治疗后局部免疫原性提高,抗肿瘤效应细胞浸润增加。展开更多
Objective: To elucidate the role and prognostic significance of lymphocyte activation-gene-3(LAG-3) in soft tissue sarcoma(STS).Methods: The expression of LAG-3 in patient and matched normal blood samples was analyzed...Objective: To elucidate the role and prognostic significance of lymphocyte activation-gene-3(LAG-3) in soft tissue sarcoma(STS).Methods: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3^+ cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3^+ T, CD4^+ T, and CD8^+ T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model.Results: Peripheral CD8^+ and CD4^+ T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors.LAG-3 expression in STS was significantly associated with a poor clinical outcome(P = 0.038) and was correlated with high pathological grade(P < 0.001), advanced tumor stage(P = 0.016). Additionally, LAG-3 expression was highly correlated with CD8^+ T-cell infiltration(r = 0.7034, P < 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8^+ and CD4^+ T cells.Conclusions: LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.展开更多
文摘目的探讨三阴型乳腺癌(triple negative breast cancer,TNBC)间质肿瘤浸润淋巴细胞(stromal tumor-infiltrating lymphocytes,sTILs)程序性死亡配体-1(programmed death ligand-1,PD-L1)蛋白的表达及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs亚群与临床病理特征的相关性及对患者预后的影响。方法收集遵义医科大学附属医院2015~2019年病理资料完善的女性TNBC标本92例,评估每张HE切片肿瘤区域内sTILs的浸润密度,采用免疫组化EnVision法检测92例TNBC中sTILs的PD-L1蛋白表达情况及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs的浸润密度。结果TNBC中sTILs与Ki-67指数(P=0.001)显著相关;CD4^(+)、CD8^(+)sTILs与肿瘤大小(P=0.012、0.006)和Ki-67指数(P=0.047、0.006)显著相关;Foxp3^(+)sTILs、PD-L1^(+)sTILs与组织学分级(P=0.001、0.005)显著相关。TNBC中sTILs与CD4^(+)、CD8^(+)sTILs呈正相关(P<0.05),与PD-L1^(+)sTILs存在显著相关性(P<0.05),与Foxp3^(+)sTILs无相关性。TNBC预后的单因素和多因素分析发现,PD-L1^(+)sTILs和淋巴结转移阳性患者具有更短的总生存期,而sTILs及CD4^(+)、CD8^(+)、Foxp3^(+)sTILs与患者的预后无相关性。结论TNBC中sTILs及CD4^(+)、CD8^(+)sTILs浸润密度可能与乳腺癌肿瘤细胞增殖有关,Foxp3^(+)sTILs可能与乳腺癌肿瘤细胞分化程度有关,而PD-L1^(+)sTILs和淋巴结转移阳性可能与TNBC的不良预后相关。
文摘目的对原发性肝癌(hepatocellu lar carc inom a,HCC)射频消融治疗(rad iofrequency ab lation,RFA)前后肿瘤内部及边缘热休克蛋白70(heat shock prote in,HSP70)的表达、CD8+T细胞数量的变化以及RFA治疗后,肿瘤边缘HSP70表达与肿瘤边缘CD8+T细胞数量之间的关系进行观察,探讨RFA治疗对原发性肝癌局部免疫功能状态的影响及其可能的临床意义。方法对17例HCC分别在RFA治疗前、后1个月,于肿瘤内部和肿瘤边缘超声引导下穿刺活检取样;采用PowerV isionTM二步染色法进行免疫组化分析,测定HSP70的表达、CD8+T细胞的数量;随访HCC复发/新生情况。结果RFA治疗后肿瘤边缘组织HSP70表达增强(Z=3.337,P=0.001)、CD8+T细胞数量增多(Z=1.996,P=0.049);RFA治疗后,≤4 cm肿瘤组的占位边缘CD8+T细胞数量高于>4 cm肿瘤组(Z=1.966,P=0.048)。RFA治疗后,边缘组织HSP70表达与CD8+T细胞数量之间呈正相关关系(r=0.489,P=0.046);RFA治疗后,无复发或新生组的占位边缘组织HSP70表达和CD8+T细胞数量分别高于复发或新生组(Z=2.009,P=0.045;Z=2.007,P=0.045)。结论RFA治疗后边缘HSP70表达增强、CD8+T细胞数量增多,显示RFA治疗后局部免疫原性提高,抗肿瘤效应细胞浸润增加。
基金supported by grants from the National Key R & D Program of China (Grant No. 2017YFA0505600-04)National Natural Science Foundation of China (Grant No. 81372887, 81572403, and 81772863)
文摘Objective: To elucidate the role and prognostic significance of lymphocyte activation-gene-3(LAG-3) in soft tissue sarcoma(STS).Methods: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3^+ cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3^+ T, CD4^+ T, and CD8^+ T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model.Results: Peripheral CD8^+ and CD4^+ T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors.LAG-3 expression in STS was significantly associated with a poor clinical outcome(P = 0.038) and was correlated with high pathological grade(P < 0.001), advanced tumor stage(P = 0.016). Additionally, LAG-3 expression was highly correlated with CD8^+ T-cell infiltration(r = 0.7034, P < 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8^+ and CD4^+ T cells.Conclusions: LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.
