消化道肿瘤 CAR-T 细胞治疗研究进展

摘要

嵌合抗原受体（CAR）-T 细胞疗法是近年来肿瘤免疫治疗领域的重大突破。该技术通过基因工程手段将患者自体T 细胞改造为能够特异识别肿瘤相关抗原的效应细胞，从而在体内实现对肿瘤细胞的精准杀伤，已在多种血液系统恶性肿瘤中取得显著疗效。然而，在消化道肿瘤等实体瘤中的应用仍面临诸多挑战，包括肿瘤抗原异质性、靶向相关非肿瘤毒性（OTOT）、T 细胞浸润与持续性不足及免疫抑制性肿瘤微环境等问题，限制了其在消化道肿瘤等实体瘤中的治疗效果。近年来，围绕CAR 结构优化、多靶点识别、基因编辑、联合治疗及微环境调控等方向的研究不断获得突破，为提升CAR-T 细胞疗法在实体瘤中的疗效提供了新的思路和策略。就CAR-T细胞疗法在消化道肿瘤中的最新研究进展进行综述，重点探讨其面临的主要障碍及相应的解决途径，并对未来发展方向进行展望。

关键词

消化道肿瘤 / CAR-T细胞疗法 / 肿瘤免疫治疗 / 肿瘤微环境 / 实体瘤

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基金资助

国家自然科学基金面上项目(32370837)

国家自然科学基金面上项目(32571072)

国家自然科学基金专项项目(T2541067)