加州大学Michel DuPage团队取得一项新突破。他们报道了细菌抗肿瘤免疫治疗有益与有害作用的细胞机制。相关论文于2025年6月5日发表于国际顶尖学术期刊《免疫学》杂志上。

研究小组我们使用一种缺乏肿瘤抗原的单核细胞增生李斯特菌减毒株（ΔactA，Lm）来检测静脉注射（i.v.）、瘤内注射（i.t.）或联合静脉注射+i.t.Lm给药后荷瘤小鼠对Lm本身的免疫反应。Lm单独将中性粒细胞招募到肿瘤中，使其具有免疫抑制作用，为Lm在肿瘤中的长期存在提供了细胞内蓄水池，促进了肿瘤的生长。相比之下，之前的静脉注射Lm产生了抗Lm细胞毒性CD8⁺T细胞，这些细胞在静脉注射Lm后浸润肿瘤。这些Lm特异性CD8⁺ T细胞通过诱导癌细胞凋亡、限制癌细胞增殖和增强肿瘤抗原向肿瘤特异性T细胞的交叉递呈来控制肿瘤。因此，针对Lm定殖肿瘤的抗Lm CD8⁺T细胞反应可以控制癌症，为利用靶向i.T.细菌的全身CD8⁺T淋巴细胞免疫的癌症免疫疗法提供了范例。

据介绍，通过基因工程将肿瘤抗原表达为癌症疫苗的细菌产生了不同的结果。

附：英文原文

Title: Cellular mechanisms underlying beneficial versus detrimental effects of bacterial antitumor immunotherapy

Author: Jesse Garcia Castillo, Sebastian Fernandez, Timothy Campbell, Diego Gonzalez Ventura, Jacob Williams, Julia Ybarra, Nicole Flores Hernandez, Elina Wells, Daniel A. Portnoy, Michel DuPage

Issue&Volume: 2025-06-05

Abstract: Bacteria engineered to express tumor antigens as cancer vaccines have produced mixed results. Here, we used an attenuated strain of Listeria monocytogenes (ΔactA, Lm) that lacks tumor antigens to examine the immune response to Lm itself in tumor-bearing mice following intravenous (i.v.), intratumoral (i.t.), or combined i.v. + i.t. Lm delivery. Unexpectedly, i.t. Lm alone recruited neutrophils to tumors, which became immunosuppressive, provided an intracellular reservoir for long-term persistence of Lm in tumors, and promoted tumor growth. In contrast, prior i.v. Lm administration generated anti-Lm cytotoxic CD8+ T cells that infiltrated tumors upon i.t. Lm delivery. These Lm-specific CD8+ T cells control tumors by inducing cancer cell apoptosis, limiting cancer cell proliferation, and enhancing tumor antigen cross-presentation to tumor-specific T cells. Thus, an anti-Lm CD8+ T cell response against Lm-colonized tumors can control cancer, offering a paradigm for cancer immunotherapy that leverages systemic CD8+ T cell immunity targeting i.t. bacteria.

DOI: 10.1016/j.immuni.2025.05.001

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00194-3