溶瘤病毒（OV）是一种增加免疫浸润到冷肿瘤的有吸引力的方法。虽然 OV 被设计为选择性感染肿瘤细胞，但有证据表明它们可以感染肿瘤中的其他非恶性细胞。我们试图确定溶瘤痘苗病毒 (VV) 是否可以感染肿瘤中的淋巴细胞，如果可以，这与治疗效果有何关系。为了研究 VV 对淋巴细胞的感染，我们在小鼠头颈部使用了 GFP 报告 VV鳞状细胞癌肿瘤模型。我们还进行了体外感染研究，以确定 VV 淋巴细胞感染 VV 的机制和后果。我们的研究结果表明，在瘤内治疗后，VV 具有感染部分免疫细胞（尤其是 T 细胞）的能力。值得注意的是，这种感染优先于往往处于缺氧状态的终末分化 T 细胞。 T 细胞的感染导致 T 细胞产生病毒以及这些细胞的最终死亡。使用在所有 T 细胞中过表达抗凋亡蛋白 Bcl2 的小鼠模型，我们发现，与同窝对照小鼠相比，MEER 肿瘤中 VV 感染后 T 细胞死亡的减少减少了完全消退的数量并缩短了生存时间。这些发现表明 OV 是治疗后不仅能够感染恶性细胞，而且这种感染可能是 OV 机制的重要组成部分。我们发现，耗尽的 CD8 T 细胞和调节性 CD4 T 细胞在治疗后的早期时间点优先被感染，并随后死亡。当 T 细胞中的细胞死亡减轻时，小鼠对 VV 治疗的反应较差，这表明删除这些群体对于 VV 的治疗反应至关重要。© 作者（或其雇主）2024。 重复使用经 CC BY-NC 许可。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Oncolytic viruses (OVs) are an attractive way to increase immune infiltration into an otherwise cold tumor. While OVs are engineered to selectively infect tumor cells, there is evidence that they can infect other non-malignant cells in the tumor. We sought to determine if oncolytic vaccinia virus (VV) can infect lymphocytes in the tumor and, if so, how this was linked to therapeutic efficacy.To investigate infection of lymphocytes by VV, we used a GFP reporting VV in a murine head and neck squamous cell carcinoma tumor model. We also performed in vitro infection studies to determine the mechanism and consequences of VV lymphocyte infection by VV.Our findings show that VV carries the capacity to infect proportions of immune cells, most notably T cells, after intratumoral treatment. Notably, this infection is preferential to terminally differentiated T cells that tend to reside in hypoxia. Infection of T cells leads to both virus production by the T cells as well as the eventual death of these cells. Using a mouse model which overexpressed the antiapoptotic protein Bcl2 in all T cells, we found that reducing T cell death following VV infection in MEER tumors reduced the number of complete regressions and reduced survival time compared with littermate control mice.These findings suggest that OVs are capable of infecting more than just malignant cells after treatment, and that this infection may be an important part of the OV mechanism. We found that exhausted CD8+ T cells and regulatory CD4+ T cells were preferentially infected at early timepoints after treatment and subsequently died. When cell death in T cells was mitigated, mice responded poorly to VV treatment, suggesting that the deletion of these populations is critical to the therapeutic response to VV.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.