肿瘤细胞治疗研究
英文原题：Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial.
这些数据表明，单一溶瘤病毒治疗能够扩增预先存在的T细胞克隆，并触发针对GBM的持久性T细胞介导免疫。
近期一项首次人体临床试验表明，胶质母细胞瘤（GBM）患者在接受rQNestin34.5v.2溶瘤病毒治疗后，其生存与免疫激活特征相关。该研究已在ClinicalTrials.gov注册（NCT03152318）。在此，我们提供了原位证据，证明单次治疗后晚期时间点仍存在持续的T细胞介导的针对肿瘤细胞的细胞毒性，且T细胞深度且持久地浸润肿瘤区域。裂解的caspase-3+肿瘤细胞与颗粒酶B+T细胞之间距离较短与治疗后更长的无进展生存期相关。预先存在的肿瘤浸润T细胞在治疗后局部扩增，与患者更长的总生存期相关。具有早期激活程序的T细胞与肿瘤细胞密切相互作用，并在治疗后强烈富集。病毒残余局限于坏死区域，而T细胞则深入浸润到存活肿瘤区域。这些数据表明，单次溶瘤病毒治疗可以扩增预先存在的T细胞克隆，并触发针对GBM的持久T细胞介导免疫。
A recent first-in-human clinical trial demonstrated that survival in glioblastoma (GBM) patients following rQNestin34.5v.2 oncolytic virus treatment was associated with immune activation signatures. This study was registered at ClinicalTrials.gov (NCT03152318). Here, we provide in situ evidence of ongoing T cell-mediated cytotoxicity against tumor cells at late time points following single treatment, with deep and persistent T cell infiltration into tumor regions. Shorter distances between cleaved caspase-3 + tumor cells and granzyme B + T cells were associated with longer progression-free survival following treatment. Pre-existing tumor-infiltrating T cells expanded locally upon treatment, correlating with longer overall patient survival. T cells with an early activation program closely interacted with tumor cells and were strongly enriched upon treatment. Viral remnants were restricted to necrotic regions, while T cells infiltrated deeply into live tumor regions. These data demonstrate that single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against GBM.
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