Maffezzini Martina, Musio Silvia, Di Ianni Natalia, Rumolo Agnese, Patanè Monica, Galluzzo Andrea, Sambruni Irene, Berlendis Arianna, Aquino Domenico, Baso Giacomo, Zingarelli Manuela, Facciolla Manuel, Maddaloni Luisa, Valentino Rossella, Paterra Rosina, Agistri Fabio, Farinotti Mariangela, Mattei Luca, Coluccia Paola, Acerbi Francesco, DiMeco Francesco, Pollo Bianca, Silvani Antonio, Eoli Marica, Traversari Catia, Montagna Daniela, Pellegatta Serena
Unit of Immunotherapy of Brain Tumors, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Unit of Neuroncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Nat Commun. 2025 Aug 25;16(1):7279. doi: 10.1038/s41467-025-62263-2.
Tumor-infiltrating lymphocyte (TIL)-therapy has received FDA approval for the treatment of advanced melanoma and shows potential for broader applications in solid tumors, including glioblastoma. In this study, tumor-reactive TILs (tr-TILs) are isolated and enriched for CD137 expression from cavitron ultrasonic aspirator (CUSA) emulsions of 161 adult patients diagnosed with diffuse gliomas. Tr-TILs are successfully expanded in 87 out of the 161 patients, reflecting an expansion rate of 54%. Notably, the presence of IDH1 mutation and the cumulative dose of steroids are identified as significant negative predictors of expansion efficacy. The expanded tr-TILs exhibit distinct phenotypic and molecular dysfunctional features yet show upregulated expression of progenitor/memory-like markers and polyclonal T-cell receptors. Importantly, these tr-TILs demonstrate specific antitumor reactivity against autologous tumor cells in both in vitro and in vivo xenograft models. These findings provide a compelling background for a personalized immunotherapeutic approach while tackling one of the most significant challenges in oncology.
肿瘤浸润淋巴细胞（TIL）疗法已获得美国食品药品监督管理局（FDA）批准用于治疗晚期黑色素瘤，并显示出在包括胶质母细胞瘤在内的实体瘤中更广泛应用的潜力。在本研究中，从161例被诊断为弥漫性胶质瘤的成年患者的超声吸引器（CUSA）乳剂中分离并富集肿瘤反应性TIL（tr-TIL）以检测CD137表达。161例患者中有87例tr-TIL成功扩增，扩增率为54%。值得注意的是，IDH1突变的存在和类固醇的累积剂量被确定为扩增疗效的显著负性预测指标。扩增后的tr-TIL表现出独特的表型和分子功能障碍特征，但祖细胞/记忆样标志物和多克隆T细胞受体的表达上调。重要的是，这些tr-TIL在体外和体内异种移植模型中均显示出对自体肿瘤细胞的特异性抗肿瘤反应性。这些发现为个性化免疫治疗方法提供了令人信服的背景，同时也应对了肿瘤学中最重大的挑战之一。
