DataVXAdvanced SciencePaper
journal article·2025-09Open access

CXCL13 Expression Promotes CAR T Cell Antitumor Activity and Potentiates Response to PD‐1 Blockade

Yang Zhou, Wenli Zhao, Yihan Zhu, Hongyan Liu, Yicheng Sun, Zhengrong Gong, Xuanyi Li, Ziying Liu, Kang Wen, Yicheng Wang, Jie Ren, Ruipei Xiao, Ling Jiang, Yanfeng Hu, Enguang Bi, Xiaoyong Zhang

Advanced Science· Volume 12· Issue 33
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Source abstract

Abstract

Abstract Immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR) T cell therapies have revolutionized cancer immunotherapy, offering significant benefits across various cancers. However, challenges remain, particularly in solid tumors where immunosuppressive tumor microenvironments and T cell exhaustion limit effectiveness. Combining ICB with CAR T cell therapy has shown potential but requires further optimization for effective synergy. Here, the bioinformatic analysis identified that CXCL13 expression is highly elevated in T cells from patients who respond to ICB, indicating its possible role in enhancing T cell antitumor responses. Mouse CAR T cells are engineered to overexpress CXCL13 and observed that these cells displayed reduced exhaustion, increased central memory phenotype, and improved mitochondrial function and proliferation in an AKT‐mTOR dependent manner. CXCL13‐overexpressing CAR T cells show significantly increased antitumor activity in vivo, particularly when combined with PD‐1 inhibition, promoting the expansion and persistence of early exhausted CD8 + CAR T cells. CXCL13 also conferred similar in vitro phenotypic enhancements in human CAR T cells as observed in murine cells. These results indicate that CXCL13 expression improves CAR T cell function and responsiveness to ICB, offering a promising and translationally relevant strategy to optimize CAR T cell therapy for solid tumors in clinical settings.
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Research context

OpenAlex topics: CAR-T cell therapy research · Immunotherapy and Immune Responses · Immune Cell Function and Interaction

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of General Surgery Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor Nanfang Hospital Southern Medical University Guangzhou 510515 China

Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China

Department of Infectious Diseases Nanfang Hospital Southern Medical University Guangzhou 510515 China

State Key Laboratory of Organ Failure Research Key Laboratory of Infectious Diseases Research in South China Ministry of Education Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases Guangdong Provincial Clinical Research Center for Viral Hepatitis Guangdong Institute of Hepatology Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology Guangzhou 510515 China

Department of Urology Zhujiang Hospital Southern Medical University Guangzhou 510282 China

Department of Hematology Nanfang Hospital Southern Medical University Guangzhou 510515 China

Guangdong Provincial Key Laboratory of Single‐cell and Extracellular Vesicles Southern Medical University Guangzhou 510515 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Basic and Applied Basic Research Foundation of Guangdong Province

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