肿瘤细胞治疗研究
英文原题：Bursting Tumor Bubbles to Improve CAR T-cell Therapy.
嵌合抗原受体（CAR）T 细胞在 B 细胞恶性肿瘤中取得了显著成功，但这一疗效尚未转化至更常见的实体瘤。
嵌合抗原受体（CAR）T 细胞在 B 细胞恶性肿瘤中取得了显著成功，但这种疗效尚未扩展到更常见的实体瘤。在本期《Cancer Research》中，Zhong 及其同事发现，肿瘤来源的小细胞外囊泡（sEV）含有间皮素等 CAR 靶抗原，因此能够在体内优先与 CAR-T 细胞相互作用并抑制其活性。CAR-T 输注后，肿瘤来源 sEV 中的 PD-L1 增加，并引发依赖 PD-L1 的 CAR-T 抑制；阻断 PD-L1 可完全逆转这一抑制。通过遗传操作肿瘤细胞或药理学方式抑制 sEV 分泌，显著改善了 CAR-T 在体内的积聚、功能和抗肿瘤活性，提示以治疗方式靶向 sEV 分泌可能成为提高 CAR-T 疗效的一种有前景的新策略。相关研究见 Zhong 等人发表的文章，第 2790 页。
Chimeric antigen receptor (CAR) T cells have had dramatic success in B-cell malignancies, but this efficacy has not yet translated to more common solid tumors. In this issue of Cancer Research, Zhong and colleagues demonstrated that tumor-derived small extracellular vesicles (sEV) contain CAR target antigens like mesothelin, enabling them to preferentially interact with and suppress the activity of CAR T cells in vivo. PD-L1 in tumor-derived sEVs increased upon CAR T-cell infusion and induced PD-L1-dependent suppression of CAR T cells that could be completely reversed by PD-L1 blockade. Strategies to inhibit sEV secretion, via genetic manipulation of tumor cells or pharmacologic inhibition, significantly improved CAR T-cell accumulation, function, and antitumor activity in vivo, suggesting that therapeutic targeting of sEV secretion could be a promising new approach to improving the efficacy of CAR T-cell therapy. See related article by Zhong et al., p. 2790.
MEMBER ACCOUNT
登录成功会直接打开下一页。
