肿瘤细胞治疗研究
英文原题：Polyclonal expansion of functional tumor-reactive lymphocytes infiltrating glioblastoma for personalized cell therapy.
Tr-TILs 在 161 例患者中的 87 例中成功扩增，扩增率为 54%。
TIL 疗法已获 FDA 批准用于晚期黑色素瘤，并显示拓展至胶质母细胞瘤等实体瘤的潜力。本研究从 161 例成人弥漫性胶质瘤患者的超声吸引器（CUSA）乳化样本中分离肿瘤反应性 TIL（tr-TIL），并富集表达 CD137 的细胞。161 例患者中有 87 例成功扩增 tr-TIL，扩增率为 54%。值得注意的是，IDH1 突变和累积类固醇剂量是扩增效果显著的负向预测因素。扩增后的 tr-TIL 具有独特表型和分子功能障碍特征，但祖细胞/记忆样标志物表达上调，且 TCR 为多克隆。重要的是，这些 tr-TIL 在体外和体内异种移植模型中均表现出针对自体肿瘤细胞的特异性抗肿瘤反应。这些发现为个体化免疫治疗策略提供了有力依据，同时针对肿瘤学中最具挑战性的问题之一。
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.
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