Harnessing NKG2D CAR-T cells with radiotherapy: a novel approach for esophageal squamous cell carcinoma treatment

作者：Tianyu Liu, Liyuan Fan, Weicheng Huang, Pengxiang Chen, Yuchen Liu, Shuyun Wang, Kaiyue Guo, Yufeng Cheng, Yali Han · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1589379 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers

Background Esophageal squamous cell carcinoma (ESCC) represents a highly aggressive malignancy with poor prognosis and limited therapeutic advancements. While chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cancer treatment, its application in ESCC remains poorly explored. This study pioneers the exploration of natural killer group 2 member D (NKG2D) CAR-T cells combined with radiotherapy for treating ESCC, with the goals of establishing a novel treatment strategy and achieving superior tumor control through combined immunoradiotherapy Methods Flow cytometry and quantitative real-time PCR (qRT-PCR) were carried out to evaluate the expression of NKG2D ligands at the cell surface protein and mRNA levels. Cell-based bioluminescence assays and enzyme-linked immunosorbent assays (ELISAs) were performed to measure the cytotoxicity and cytokine secretion of NKG2D CAR-T cells. A human ESCC subcutaneous xenograft model and a bilateral xenograft model were established. Luminex liquid suspension chip detection was utilized to verify the changes in cytokines and chemokines in the circulation and at tumor sites. Immunohistochemical analysis was conducted to assess the accumulation of T cells in vivo . Results NKG2D ligands are widely expressed in ESCC cell lines and can be further increased by irradiation at both the mRNA and cell surface protein levels. NKG2D CAR-T cells efficiently recognized and lysed ESCC cell lines, and irradiation enhanced the activity of NKG2D CAR...