文章：

溶瘤病毒促进肿瘤反应性浸润淋巴细胞过继细胞治疗

Oncolytic virus promotes tumor-reactive infiltrating lymphocytes for adoptive cell therapy 

原文发布日期：2020-07-07 

英文摘要：

Adoptive cell therapy (ACT) using tumor-specific tumor-infiltrating lymphocytes (TILs) has demonstrated success in patients where tumor-antigen specific TILs can be harvested from the tumor, expanded, and re-infused in combination with a preparatory regimen and IL2. One major issue for non-immunogenic tumors has been that the isolated TILs lack tumor specificity and thus possess limited in vivo therapeutic function. An oncolytic virus (OV) mediates an immunogenic cell death for cancer cells, leading to elicitation and dramatic enhancement of tumor-specific TILs. We hypothesized that the tumor-specific TILs elicited and promoted by an OV would be a great source for ACT for solid cancer. In this study, we show that a local injection of oncolytic poxvirus in MC38 tumor with low immunogenicity in C57BL/6 mice, led to elicitation and accumulation of tumor-specific TILs in the tumor tissue. Our analyses indicated that IL2-armed OV-elicited TILs contain lower quantities of exhausted PD-1hiTim-3+ CD8+ T cells and regulatory T cells. The isolated TILs from IL2-expressing OV-treated tumor tissue retained high tumor specificity after expansion ex vivo. These TILs resulted in significant tumor regression and improved survival after adoptive transfer in mice with established MC38 tumor. Our study showcases the feasibility of using an OV to induce tumor-reactive TILs that can be expanded for ACT. 

摘要翻译： 

采用肿瘤特异性肿瘤浸润淋巴细胞（TIL）的过继细胞疗法（ACT）已在特定患者群体中取得显著疗效——这些患者的肿瘤抗原特异性TIL能够从肿瘤组织中提取、扩增，并与预处理方案及IL2联合回输。但对于非免疫原性肿瘤，核心难题在于分离的TIL缺乏肿瘤特异性，导致体内治疗功能受限。溶瘤病毒（OV）可介导癌细胞的免疫原性死亡，从而激发并显著增强肿瘤特异性TIL的活性。我们提出假设：经OV激发促进的肿瘤特异性TIL将成为实体瘤ACT治疗的优质细胞来源。本研究表明，在C57BL/6小鼠低免疫原性MC38肿瘤模型中局部注射溶瘤痘病毒，可有效激发肿瘤特异性TIL并在肿瘤组织中聚集。分析显示，IL2修饰的OV所激发的TIL中，耗竭型PD-1hiTim-3+ CD8+ T细胞和调节性T细胞含量较低。从表达IL2的OV处理肿瘤组织中分离的TIL，在体外扩增后仍保持高度肿瘤特异性。这些TIL过继转移至已建立MC38肿瘤的小鼠体内后，可显著诱导肿瘤消退并延长生存期。本研究证实了利用OV诱导肿瘤反应性TIL并扩增用于ACT的可行性。

原文链接：

Oncolytic virus promotes tumor-reactive infiltrating lymphocytes for adoptive cell therapy