Xu JJ, Ni CX, Qin LD, Wang P, Xu JJ. Cryoablation remodels the immune microenvironment in hepatocellular carcinoma: From mechanistic insights to clinical translation in combination immunotherapy. World J Gastrointest Oncol 2026; 18(6): 118976 [DOI: 10.4251/wjgo.v18.i6.118976]
Corresponding Author of This Article
Jia-Ju Xu, MD, Department of Medical Oncology, Tai’an City Central Hospital, No. 29 Longtan Road, Tai’an 271000, Shandong Province, China. jiajuxu1101@163.com
Research Domain of This Article
Oncology
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review-article
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Xu JJ, Ni CX, Qin LD, Wang P, Xu JJ. Cryoablation remodels the immune microenvironment in hepatocellular carcinoma: From mechanistic insights to clinical translation in combination immunotherapy. World J Gastrointest Oncol 2026; 18(6): 118976 [DOI: 10.4251/wjgo.v18.i6.118976]
World J Gastrointest Oncol. Jun 15, 2026; 18(6): 118976 Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.118976
Cryoablation remodels the immune microenvironment in hepatocellular carcinoma: From mechanistic insights to clinical translation in combination immunotherapy
Jia-Ju Xu, Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China
Chun-Xiao Ni, Department of Minimally Invasive Oncology, Tai’an City Central Hospital, Tai’an 271000, Shandong Province, China
Li-Dong Qin, Ping Wang, Jia-Ju Xu, Department of Medical Oncology, Tai’an City Central Hospital, Tai’an 271000, Shandong Province, China
Co-first authors: Jia-Ju Xu and Chun-Xiao Ni.
Author contributions: Xu JJ and Ni CX contribute equally to this study, played essential roles in the critical stages of research design, data collection and analysis, and manuscript preparation as co-first authors; Xu JJ drafted the initial manuscript; Ni CX collected, analyzed the data, and contributed to the discussion of results; Qin LD and Wang P assisted in data collection and analysis; Xu JJ conceived and designed the review and critically revised the manuscript for important intellectual content.
Supported by the Scientific Research Fund of Tai’an Science and Technology Agency, No. 2019NS180.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Jia-Ju Xu, MD, Department of Medical Oncology, Tai’an City Central Hospital, No. 29 Longtan Road, Tai’an 271000, Shandong Province, China. jiajuxu1101@163.com
Received: January 16, 2026 Revised: February 4, 2026 Accepted: February 11, 2026 Published online: June 15, 2026 Processing time: 145 Days and 2.9 Hours
Abstract
Hepatocellular carcinoma remains a persistent therapeutic challenge, in part due to an immunosuppressive tumor microenvironment that renders it a “cold” tumor and limits the efficacy of immune checkpoint inhibitors. Local cryoablation transcends its direct cytotoxic role by eliciting systemic immunomodulatory effects. This review discussed the dual role of cryoablation in reprogramming the hepatocellular carcinoma tumor microenvironment. Mechanistically: Cryoablation induces immunogenic cell death, which serves as an in situ vaccine to release tumor antigens and danger signals to activate dendritic cells and prime tumor-specific T-cell responses. Nonetheless, this immunogenic response is normally offset by an attendant, transient immunosuppressive backlash. We review the preclinical and clinical data on the combination of cryoablation and immune checkpoint inhibitors, and a strategy that is aimed at blocking this inhibitory feedback and synergistically transforming the so-called “cold” tumors into immunologically “hot” tumors. The completeness of ablation, technical parameters and the host immune status are key determinants of therapeutic outcome. Current translational issues, especially with regard to stratification of patients, are discussed. Future progress of this promising combinatorial strategy will depend on the development of predictive biomarkers and on fine-tuning of combination regimens.
Core Tip: Cryoablation exerts a dual and exploitable immunomodulatory effects in hepatocellular carcinoma. Acting as an in situ vaccine, cryoablation induces immunogenic cell death and simultaneously triggers a transient immunosuppressive effect. This duality is strategically used by combining cryoablation with immune checkpoint inhibitors to remodel the immunosuppressive “cold” tumor microenvironment. Ablation completeness, technical parameters, and host immune status are critical determinants of therapeutic success. In order to fully achieve its clinical potential, future initiatives ought to be directed towards overcoming the difficulties of patient stratification and treatment sequencing by developing predictive biomarkers and optimized combination regimens.
