尽管努力改进标准干预措施，结直肠癌（CRC）仍然是癌症相关死亡的主要原因。由于 CRC 患者可以受益于激发效应 T 细胞作用的免疫治疗策略，因此癌症疫苗代表了一种安全且有前景的治疗方法，可引发针对肿瘤微环境 (TME) 成分的保护性且持久的免疫反应。在这项研究中，我们研究了基于单核细胞增生李斯特菌 (Lm) 的疫苗针对 CRC 相关脉管系统的临床前潜力。 CRC 的生存和进展依赖于功能正常的血管来有效介导各种代谢过程并为底层组织供氧。因此，我们提出了在同系小鼠模型中启动针对内源性周细胞抗原 RGS5 的免疫的策略，RGS5 是病理性血管化的关键介质。总体而言，基于 Lm 的疫苗接种可以安全地诱导有效的抗肿瘤作用，包括将功能性 1 型相关 T 细胞募集到 TME 中并减少肿瘤血管含量。这项研究强调了以 RGS5 为靶点对抗 CRC 等血管化肿瘤的广阔临床潜力。© 2023 作者。经泰勒许可出版

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.