胃癌中TGF-β、PD-L1表达与肿瘤免疫表型的关系及其临床意义

Correlation of the Expression of TGF-β and PD-L1 and Cancer-immune Phenotypes in Gastric Cancer and Its Clinical Significance

关键词:  胃癌  免疫卡控点阻断治疗(ICB)  肿瘤免疫表型  TGF-β  PD-L1

Key words:  gastric cancer  ICB  cancer-immune phenotypes  TGF-β  PD-L1

摘要:

目的 检测TGF-β、PD-L1在胃癌患者中的表达情况，并探讨两者表达与肿瘤免疫表型的关系及其临床意义。方法 收集南京医科大学连云港临床医学院2017—2019年84例行胃癌切除术患者的肿瘤石蜡组织标本及其对应的临床病例特征。采用免疫组织法检测其中PD-L1、TGF-β和CD8⁺T细胞的表达，采用GraphPad Prism7和SPSS 21.0统计软件分析TGF-β、PD-L1表达与肿瘤免疫表型的关系及其临床意义。结果 TGF-β在胃癌中的阳性表达率为76.2%，PD-L1在胃癌中的阳性表达率为79.7%。免疫炎症型、免疫豁免型、免疫沙漠型3种免疫表型在胃癌中的表达率分别为33.3%，51.2%及15.5%。胃癌中3种免疫表型之间TGF-β表达水平差异具有统计学意义（P<0.05）。其中，胃癌中免疫豁免型与TGF-β表达水平呈显著正相关（P<0.05）。胃癌中3种免疫表型之间PD-L1表达水平差异无统计学意义。胃癌中TGF-β表达和PD-L1表达正相关（P<0.05）。胃癌中TGF-β表达与淋巴结转移（P<0.05）、TNM分期（P<0.05）密切相关。胃癌中PD-L1表达与浸润程度（P<0.05）、淋巴结转移（P<0.05）、TNM分期（P<0.05）密切相关。免疫豁免型与肿瘤直径密切相关（P<0.05）。结论 胃癌中TGF-β和PD-L1均有表达，且胃癌中TGF-β表达与PD-L1表达呈显著正相关。胃癌中TGF-β和胃癌肿瘤免疫表型显著相关，TGF-β高表达患者多为免疫豁免型。而胃癌中PD-L1表达与胃癌肿瘤免疫表型无显著相关性。胃癌中TGF-β、PD-L1表达和肿瘤免疫表型与部分临床病理特征（肿瘤侵袭程度、淋巴结转移、TNM分期、肿瘤直径等）密切相关。

Abstract:

OBJECTIVE To detect the expression of TGF-β and PD-L1 in gastric cancer, and to explore the relationship between them and cancer-immune phenotypes and their clinical significance. METHODS The paraffin tissue samples and clinicopathologic features of 84 patients who underwent gastrectomy in Lianyungang Clinical Medical College of Nanjing Medical University from 2017 to 2019 were collected. The expression of PD-L1, TGF-β and CD8⁺T cells was detected by immunohistochemistry method. The relationship between the expression of TGF-β, PD-L1 and cancer-immune phenotypes and their clinical significance was analyzed by GraphPad Prism7 and SPSS 21.0 statistical software. RESULTS The positive expression rate of TGF-β and PD-L1 in gastric cancer were 76.2% and 79.7% respectively. The immunophenotypes of immune-inflamed, immune-excluded and immune-desert in gastric cancer were 33.3%, 51.2% and 15.5%, respectively. There was significant difference in the expression of TGF-β among the three immunophenotypes in gastric cancer(P<0.05). Among them, there was a significant positive correlation between immune-excluded and the expression level of TGF-β in gastric cancer(P<0.05). However, there was no significant difference in the expression of PD-L1 among the three immunophenotypes in gastric cancer. The expression of TGF-β was correlated with that of PD-L1 in gastric cancer positively(P<0.05). The expression of TGF-β in gastric cancer was related to lymph node metastasis(P<0.05) and TNM stage(P<0.05) significantly. The expression of PD-L1 in gastric cancer was related to the degree of tumor invasion(P<0.05), lymph node metastasis(P<0.05) and TNM stage(P<0.05) significantly. The immune-excluded was related to the tumor diameter(P<0.05) significantly. The expression of immune-inflamed was related to the diameter of tumor(P<0.05). CONCLUSION Both TGF-β and PD-L1 are expressed in gastric cancer, and the expression of TGF-β is positively correlated with the expression of PD-L1 in gastric cancer. There is a significant positive correlation between immune-excluded and TGF-β expression in gastric cancer, and most of the patients with high expression of TGF-β were immune-excluded immunophenotypes. There is no significant correlation between PD-L1 expression and tumor immunophenotypes in gastric cancer. The expression of TGF-β, PD-L1 and tumor immunophenotypes in gastric cancer are closely related to some clinicopathological features such as the degree of tumor invasion, lymph node metastasis TNM stage and the tumor diameter.