美国Roswell Park综合癌症中心医学部Renier J. Brentjens小组的一项最新研究提出了IL-36γ修饰型CAR-T细胞重编程中性粒细胞以诱导内源性抗肿瘤免疫。相关论文发表在2025年12月11日出版的《癌细胞》杂志上。

研究人员报道IL-36γ修饰型CAR - T细胞根除原发性实体瘤，并使抗原阴性肿瘤的再挑战排斥。IL-36γ修饰型CAR- T细胞有利地调节TME和重编程独特的具有肿瘤杀伤能力和抗原（交叉）呈递功能的中性粒细胞亚群，导致诱导内源性T细胞识别肿瘤抗原而不是CAR靶向抗原。他们的研究表明，CAR - T细胞与中性粒细胞的结合是建立癌症免疫周期的关键步骤，并引入了一种广泛适用的方法来克服实体瘤过继细胞治疗的关键障碍。

据介绍，嵌合抗原受体（CAR） T细胞由于抗原异质性和免疫抑制肿瘤微环境（TME）的障碍，对实体肿瘤无效。以往的研究主要集中在增强CAR - T细胞的细胞毒性和持久性上，而利用CAR - T细胞对宿主抗肿瘤免疫的调节作用来提高其治疗效果的可行性尚不清楚。

附：英文原文

Title: IL-36γ armored CAR T cells reprogram neutrophils to induce endogenous antitumor immunity

Author: Yihan Zuo, David J. Vohwinkel, Bowen Dong, James R. McDowell, Brandon V. Guzman, Tharuna Sri Manickavel Pandian, Saborni Chattopadhyay, A.J.R. McGray, Scott H. Olejniczak, Joyce Ohm, Jianmin Wang, Mark D. Long, Eduardo Cortes Gomez, Terence J. Purdon, Wei Luo, Hemn Mohammadpour, Christopher S. Hackett, Leonid Cherkassky, Marco Davila, Scott I. Abrams, Renier J. Brentjens

Issue&Volume: 2025-12-11

Abstract: Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors due to obstacles of antigen heterogeneity and the immunosuppressive tumor microenvironment (TME). Previous efforts focused on enhancing cytotoxicity and persistence of CAR T cells, while the feasibility of improving their therapeutic efficacy by leveraging the modulatory effects of CAR T cells on host anti-tumor immunity remains unclear. Here, we report that IL-36γ armored CAR T cells eradicate primary solid tumors and enable rejection of rechallenged antigen-negative tumors. IL-36γ armored CAR T cells favorably modulate the TME and reprogram unique neutrophil subsets with tumoricidal ability and antigen-(cross) presenting functions, resulting in the induction of endogenous T cells recognizing tumor antigens beyond CAR-targeted antigens. Our study demonstrates that neutrophil engagement by CAR T cells is a critical step in the establishment of the cancer-immunity cycle and introduces a broadly applicable method to overcome key barriers to adoptive cell therapies for solid tumors.

DOI: 10.1016/j.ccell.2025.11.007

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00500-8