High expression ITGA2 affects the expression of MET, PD-L1, CD4 and CD8 with the immune microenvironment in pancreatic cancer patients

Frontiers in Immunology

Immunology

Hongbo Shi¹  Ziting Su¹  Yunbo Tan¹  Yiming Chen¹  Liquan Jin¹  Jifu Hu²  Xiaoxi Li²  Zhe Li²  Bilian Du²  Yaoqiang Duan²  Zhenqi Li² 

[1] 1St Department of General Surgery, The First Affiliated Hospital of Dali University, Dali, Yunnan, China;Clinical Medical College of Dali University, Dali, Yunnan, China;

关键词: pancreatic cancer;    ITGA2;    EMT;    PD-L1;    microenvironment;   

DOI  :  10.3389/fimmu.2023.1209367

 received in 2023-04-20, accepted in 2023-09-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

PurposePancreatic cancer is characterized by a grim prognosis and is regarded as one of the most formidable malignancies. Among the genes exhibiting high expression in different tumor tissues, ITGA2 stands out as a promising candidate for cancer therapy. The promotion of cancer in pancreatic cancer is not effective. The objective of this study is to assess the presence of ITGA2, EMT and PD-L1 in pancreatic cancer.Experimental designWe examined the expression of ITGA2, MET, E-cadherin, PD-L1, CD4, and CD8 proteins in 62 pancreatic cancer tissue samples using multi-tissue immunofluorescence and immunohistochemistry techniques. Functional assays, such as the cell migration assay and transwell assay, were used to determine the biological role of ITGA2 in pancreatic cancer. The relationship of ITGA2,EMT and PD-L1 were examined using Western blot analysis and RT-qPCR assay.ResultsIn our study, we observed the expression of ITGA2, E-cadherin, and PD-L1 in both tumor and stroma tissues of pancreatic cancer. Additionally, a positive correlation between ITGA2, E-cadherin, and PD-L1 in the tumor region (r=0.559, P<0.001 and r=0.511, P<0.001), and PD-L1 in the stroma region (r=0.512, P<0.001).The expression levels of ITGA2, CD4, and CD8 were found to be higher in pancreatic cancer tissues compared to adjacent tissues (P < 0.05). Additionally, ITGA2 was negatively correlated with CD4 and CD8 (r = -0.344, P < 0.005 and r = -0.398, P < 0.005).Furthermore, ITGA2, CD4, and CD8 were found to be correlated with the survival time of patients (P < 0.05). Blocking ITGA2 inhibited the proliferation and invasion ability of pancreatic cancer cells significantly, Additionally, sh-ITGA2 can down-regulate the expression of EMT and PD-L1.ConclusionsWe identified a novel mechanism in which ITGA2 plays a crucial role in the regulation of pancreatic cancer growth and invasion. This mechanism involves the upregulation of MET and PD-L1 expression in pancreatic cancer cells. Additionally, we found that increased expression of ITGA2 is associated with a poor prognosis in pancreatic cancer patients. Furthermore, ITGA2 also affects immune regulation in these patients. Therefore, targeting ITGA2 is an effective method to enhance the efficacy of checkpoint immunotherapy and prohibiting tumor growth against pancreatic cancer.

【 授权许可】

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Copyright © 2023 Jin, Duan, Li, Li, Hu, Shi, Su, Li, Du, Chen and Tan