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已发表论文
ITGB7 改造胰腺癌的炎症和免疫微环境并增强基于检查点抑制剂的免疫治疗
Authors Zhu Y, Lei Y, Luo A, Zhang Q, Cai L, Zhang Y, Li X, Wang B, Sun D, Li Y, Sun P, Gong S, Cheng Y
Received 15 April 2025
Accepted for publication 2 December 2025
Published 16 December 2025 Volume 2025:18 Pages 17633—17649
DOI https://doi.org/10.2147/JIR.S534605
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Ning Quan
Yun Zhu,1 Yi Lei,2 Anni Luo,1 Qingqing Zhang,2 Linqian Cai,1 Yongxin Zhang,1 Xiangzhao Li,3 Biao Wang,4 Danning Sun,1 Yanqi Li,1 Penghui Sun,5 Sitang Gong,2 Yang Cheng2
1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Digestive Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of China; 3Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 4Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
Correspondence: Yang Cheng, Department of Digestive, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Guangzhou, Guangdong, 510623, People’s Republic of China, Email chengyang2872@sina.com
Background: The role of ITGB7 in pancreatic ductal adenocarcinoma (PDAC) remains unreported. This study aims to investigate the effects of ITGB7 on inflammation and immune microenvironment, and its correlation with the response to immune checkpoint inhibitors (ICIs).
Methods: The correlation between ITGB7 expression and the response to ICIs treatment was evaluated in our clinical cohort and in the TCGA dataset. TMT and PRM proteomic analysis identified ITGB7-associated proteins, biological processes, and signal pathways. The role of ITGB7 in macrophage polarization was explored both in vivo and in vitro. Additionally, ITGB7-associated immune and inflammatory regulatory molecules, and immune cells infiltration in PDAC were assessed using TCGA dataset. An ITGB7-associated ceRNA network was constructed to explore post-transcriptional regulation.
Results: Clinical sample analysis and TCGA analysis showed that ITGB7 was significantly overexpressed in PDAC compared to normal pancreatic tissue. Patients with high ITGB7 expression demonstrated a better response to ICIs blockade therapy and exhibited a favorable prognosis. Proteomic analysis indicated that ITGB7 regulates immune- and inflammation- related proteins. ITGB7 expressed in pancreatic tumor cells promoted M2 macrophage polarization. ITGB7 modulated immune-related signaling pathways and was positively correlated with expression of immune checkpoint molecules, inflammatory cytokines, and immune-stimulating molecules. ITGB7 correlated with increased immune cell infiltration.
Conclusion: We provide the first evidence that ITGB7 expression correlates with immune regulation, inflammatory modulation, and immune cell infiltration in PDAC. ITGB7 is associated with enhanced immunotherapy response and improved prognosis. This study provides novel insights into the regulation of PDAC immune responses.
Keywords: pancreatic ductal adenocarcinoma, ITGB7, immunotherapy response, inflammatory modulation, prognosis
1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Digestive Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of China; 3Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 4Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
Correspondence: Yang Cheng, Department of Digestive, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Guangzhou, Guangdong, 510623, People’s Republic of China, Email chengyang2872@sina.com
Background: The role of ITGB7 in pancreatic ductal adenocarcinoma (PDAC) remains unreported. This study aims to investigate the effects of ITGB7 on inflammation and immune microenvironment, and its correlation with the response to immune checkpoint inhibitors (ICIs).
Methods: The correlation between ITGB7 expression and the response to ICIs treatment was evaluated in our clinical cohort and in the TCGA dataset. TMT and PRM proteomic analysis identified ITGB7-associated proteins, biological processes, and signal pathways. The role of ITGB7 in macrophage polarization was explored both in vivo and in vitro. Additionally, ITGB7-associated immune and inflammatory regulatory molecules, and immune cells infiltration in PDAC were assessed using TCGA dataset. An ITGB7-associated ceRNA network was constructed to explore post-transcriptional regulation.
Results: Clinical sample analysis and TCGA analysis showed that ITGB7 was significantly overexpressed in PDAC compared to normal pancreatic tissue. Patients with high ITGB7 expression demonstrated a better response to ICIs blockade therapy and exhibited a favorable prognosis. Proteomic analysis indicated that ITGB7 regulates immune- and inflammation- related proteins. ITGB7 expressed in pancreatic tumor cells promoted M2 macrophage polarization. ITGB7 modulated immune-related signaling pathways and was positively correlated with expression of immune checkpoint molecules, inflammatory cytokines, and immune-stimulating molecules. ITGB7 correlated with increased immune cell infiltration.
Conclusion: We provide the first evidence that ITGB7 expression correlates with immune regulation, inflammatory modulation, and immune cell infiltration in PDAC. ITGB7 is associated with enhanced immunotherapy response and improved prognosis. This study provides novel insights into the regulation of PDAC immune responses.
Keywords: pancreatic ductal adenocarcinoma, ITGB7, immunotherapy response, inflammatory modulation, prognosis