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The article reviews mechanisms of immune checkpoint inhibitors, gallbladder cancer–specific tumor microenvironment and biomarkers, summarizes relevant clinical trials and subgroup analyses, and interprets guidelines while outlining practical immunotherapy strategies for routine care.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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Safrany,  \nKeele University, United Kingdom  \nREVIEWED BY  \nXing He,  \nSun Yat-sen University, China Hitoshi Minagi,  \nOkayama University, Japan  \n*CORRESPONDENCE  \nTao Wu  \n [kmwt624@hotmail.com](kmwt624@hotmail.com)  \nRECEIVED 22 April 2026  \nREVISED 13 July 2026  \nACCEPTED 14 July 2026  \nPUBLISHED 06 August 2026  \nCITATION  \nLi F, Wang Y, Xu Z, Zhu M, Su K, Yang X and Wu T (2026) New progress and clinical research translation of immune checkpoint inhibitors in systemic therapy of gallbladder cancer.  \nFront. Immunol. 17:1862775 .  \ndoi: 10.3389/fimmu.2026.1862775  \nCOPYRIGHT  \n© 2026 Li, Wang, Xu, Zhu, Su, Yang and Wu. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nNew progress and clinical research translation of immune checkpoint inhibitors in systemic therapy of gallbladder cancer  \nFuhong Li, Yuxiao Wang, Zhiren Xu, Meng Zhu, Kun Su, Xiawei Yang and Tao Wu*  \nDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China  \nGallbladder cancer (GBC) is a highly malignant tumor of the biliary tract system.Although it is less common than other malignant tumors of the digestive system, its incidence and mortality rates have been on a continuous rise. Withinsidious early symptoms, the majority of patients are diagnosed at an advanced stage when the disease is detected. Surgical resection remains the radical treatment for gallbladder cancer yet many patients lose the opportunity for surgical intervention when seeking medical attention due to the onset of symptoms.In addition, given the high invasiveness and high recurrence rate of gallbladder cancer, systemic therapy beyond surgical treatment is particularly crucial. In recent years, precision medicine centered on immunotherapy and targeted therapy has exhibited certain therapeutic effects and improved the quality of life in patients with advanced cancer. Immunotherapy is a therapeutic modality that prevents immune evasion of tumor cells, primarily by means of immune checkpoint inhibitors such as CTLA-4 and PD- 1/PD-L1 inhibitors, among which PD-1/PD-L1 inhibitors are widely used in the immunotherapy of gallbladder cancer. Following the success of the global Phase III TOPAZ-1 and KEYNOTE-966 trials, durvalumab in combination with gemcitabine and cisplatin, as well as pembrolizumab combined with gemcitabine and cisplatin, have been approved in multiple countries and recommended by authoritative guidelines asthe preferred first-line systemic therapeutic regimens for advanced biliary tract cancers. A number of clinical trials conducted in recent years have initiated subgroup analyses of biliary tract cancer together with detections of biomarkers and the tumor microenvironment, providing guidance for immunotherapy of gallbladder cancer. This article elaborates on the mechanisms of immune checkpoint inhibitors, the unique tumor microenvironment and biomarkers specific to gallbladder cancer, summarizes clinical trials concerning gallbladder cancer and those incorporating gallbladder cancer subgroup analyses, interprets authoritative clinical guidelines and relevant policies, and presents the strategies and procedures adopted by our team for administering immunotherapy to patients with gallbladder cancer in routine clinical practice.  \nKEYWORDS  \nbiliary tract cancer, clinical decision-making, gallbladder cancer, immune checkpoint inhibitors, PD-1, PD-L1  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \n1","cbCaikJ6dgTmIyZP","https://ap.wps.com/l/cbCaikJ6dgTmIyZP","pdf",3101246,15,"English","# 1 Introduction\n# Mechanisms of immune checkpoint inhibitors\n# Tumor microenvironment and biomarkers in gallbladder cancer\n# Clinical trials and subgroup analyses\n# Interpretation of guidelines and policies\n# Practical immunotherapy strategies in routine care","[{\"question\":\"Why is systemic therapy important for gallbladder cancer beyond surgery?\",\"answer\":\"Because many patients cannot access surgical intervention and gallbladder cancer is highly invasive with a high recurrence rate, systemic therapy is crucial beyond resection.\"},{\"question\":\"Which immune checkpoint inhibitors are highlighted in gallbladder cancer immunotherapy?\",\"answer\":\"The review focuses on CTLA-4 and PD-1/PD-L1 inhibitors, noting that PD-1/PD-L1 inhibitors are widely used for gallbladder cancer.\"},{\"question\":\"What does the article cover regarding clinical evidence and translation to practice?\",\"answer\":\"It summarizes mechanisms, gallbladder cancer-specific microenvironment and biomarkers, reviews clinical trials including subgroup analyses, interprets authoritative guidelines and policies, and presents team strategies for administering immunotherapy in routine practice.\"}]","New progress and clinical research translation of immune checkpoint inhibitors in systemic therapy of gallbladder cancer | PDF",1790097591,38]