嵌合抗原受体（CAR）T细胞在B细胞性恶性肿瘤中取得了显著的成功，但其疗效尚未在更常见的实体肿瘤中得到验证。在这篇《癌症研究》杂志中，钟等同事证明了肿瘤来源的小型细胞外囊泡（sEV）含有类似介质蛋白的CAR靶向抗原，使它们能选择性地与CAR T细胞在体内相互作用并抑制其活性。肿瘤来源的sEV中的PD-L1在CAR T细胞输注后增加，并通过PD-L1阻断诱导CAR T细胞的PD-L1依赖性抑制，该抑制可完全通过PD-L1阻断解除。通过遗传操作肿瘤细胞或药理学抑制sEV分泌的策略，在体内显著改善了CAR T细胞的累积、功能和抗肿瘤活性，表明治疗性靶向sEV分泌可能是改善CAR T细胞疗法疗效的有前景的新方法。详见钟等人的相关文章，第2790页。©2023美国癌症研究协会。

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.©2023 American Association for Cancer Research.