Listeria-based vaccination against the pericyte antigen RGS5 elicits anti-vascular effects and colon cancer protection.

IF 7.2 2区医学 Oncoimmunology Pub Date : 2023-09-28 eCollection Date: 2023-01-01 DOI:10.1080/2162402X.2023.2260620

Trevor S Anderson, Amanda L McCormick, Elizabeth A Daugherity, Mariam Oladejo, Izuchukwu F Okpalanwaka, Savanna L Smith, Duke Appiah, Laurence M Wood, Devin B Lowe

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Abstract

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.

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针对周细胞抗原RGS5的基于李斯特菌的疫苗接种引起抗血管作用和结肠癌癌症保护。

尽管努力改进标准干预措施，但癌症结直肠癌（CRC）仍然是癌症相关死亡率的主要原因。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，癌症疫苗代表了一种安全且有前途的治疗方法，可以引发针对肿瘤微环境（TME）成分的保护性和持久性免疫反应。在这项研究中，我们研究了基于单核细胞增多性李斯特菌（Lm）的疫苗针对CRC相关血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地介导各种代谢过程和氧化基础组织。因此，我们提出了在同基因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是病理血管形成的关键介质。总的来说，基于Lm的疫苗接种安全地诱导了强大的抗肿瘤作用，包括将功能性1型相关T细胞募集到TME中并降低肿瘤血管含量。这项研究强调了靶向RGS5对抗CRC等血管化肿瘤的临床潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncoimmunology ONCOLOGY-IMMUNOLOGY

CiteScore

12.80

自引率

2.80%

发文量

276

期刊介绍： Tumor immunology explores the natural and therapy-induced recognition of cancers, along with the complex interplay between oncogenesis, inflammation, and immunosurveillance. In response to recent advancements, a new journal, OncoImmunology, is being launched to specifically address tumor immunology. The field has seen significant progress with the clinical demonstration and FDA approval of anticancer immunotherapies. There's also growing evidence suggesting that many current chemotherapeutic agents rely on immune effectors for their efficacy. While oncologists have historically utilized chemotherapeutic and radiotherapeutic regimens successfully, they may have unwittingly leveraged the immune system's ability to recognize tumor-specific antigens and control cancer growth. Consequently, immunological biomarkers are increasingly crucial for cancer prognosis and predicting chemotherapy efficacy. There's strong support for combining conventional anticancer therapies with immunotherapies. OncoImmunology will welcome high-profile submissions spanning fundamental, translational, and clinical aspects of tumor immunology, including solid and hematological cancers, inflammation, and both innate and acquired immune responses.