前列腺癌（PCa）被称为“冷肿瘤”，免疫反应有限，使得肿瘤对免疫检查点抑制剂（ICI）产生抵抗。治疗性信使 RNA (mRNA) 疫苗已成为一种有前途的策略，通过增强免疫反应性并显着提高抗肿瘤功效来克服这一挑战。在我们的研究中，我们合成了 Tetra（一种与多种肿瘤相关抗原混合的 mRNA 疫苗）和 ImmunER（一种免疫增强佐剂），旨在诱导有效的抗肿瘤免疫。 ImmunER 表现出促进树突状细胞 (DC) 成熟、增强 DC 迁移以及改善细胞和动物水平抗原呈递的能力。此外，Tetra 与 ImmunER 联合诱导骨髓源性树突状细胞 (BMDC) 向 cDC1-CCL22 转化，并上调 JAK-STAT1 通路，促进 IL-12、TNF-α 等细胞因子的释放。细胞因子。这种级联反应增强了 T 细胞的增殖和活化，从而有效杀死肿瘤细胞。体内实验进一步表明，Tetra  ImmunER 增加了 RM-1-PSMA 肿瘤组织中 CD8 T 细胞的浸润和活化。总之，我们的研究结果强调了 Tetra 和 ImmunER mRNA-LNP 整合疗法在 PCa 中增强抗肿瘤免疫的巨大潜力。© 2024 作者。由泰勒授权出版

Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.