Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy
Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy
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DOI：
10.1172/jci.insight.134612
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发表时间：
2020-06-18
期刊：
影响因子：
8
通讯作者：
Rodig, Scott J.
中科院分区：
文献类型：
--
作者：
Chen, Pei-Hsuan;Lipschitz, Mikel;Rodig, Scott J.
嵌合抗原受体（CAR）T细胞介导的抗肿瘤免疫和毒性的机制仍然缺乏表征，因为很少有研究检查CAR T细胞输注后的完整肿瘤微环境（TME）。Axicabtagene ciloleucel是一种获批用于大B细胞淋巴瘤患者的自体抗CD19 CAR T细胞疗法。我们设计了多重免疫染色和ISH测定来询问在axicabtagene ciloleucel输注后弥漫性大B细胞淋巴瘤的活检中的CAR T细胞和其他免疫细胞浸润。我们发现大多数肿瘤内CAR T细胞表达T细胞活化的标志物，但出乎意料的是，
Mechanisms of chimeric antigen receptor (CAR) T cell-mediated antitumor immunity and toxicity remain poorly characterized because few studies examine the intact tumor microenvironment (TME) following CAR T cell infusion. Axicabtagene ciloleucel is an autologous anti-CD19 CAR T cell therapy approved for patients with large B cell lymphoma. We devised multiplex immunostaining and ISH assays to interrogate CAR T cells and other immune cell infiltrates in biopsies of diffuse large B cell lymphoma following axicabtagene ciloleucel infusion. We found that a majority of intratumoral CAR T cells expressed markers of T cell activation but, unexpectedly, constituted