我们的研究旨在阐明半乳糖凝集素-1 (Gal-1) 在前列腺癌 (PCa) 免疫抑制肿瘤微环境 (TME) 中的作用。我们之前的研究结果表明 Gal-1 表达升高与晚期 PCa 分期之间存在相关性。在本研究中，我们还观察到Gal-1在肿瘤基质周围表达，其表达水平与PCa进展相关。我们发现PCa细胞可以分泌Gal-1，并且分泌的Gal-1具有诱导T细胞凋亡的潜力。 LLS30 敲低 Gal-1 或抑制 Gal-1 功能可抑制 T 细胞凋亡，导致瘤内 T 细胞浸润增加。重要的是，LLS30治疗显着提高了抗PD-1的体内抗肿瘤功效。从机制上讲，LLS30 与 Gal-1 的碳水化合物识别域 (CRD) 结合，破坏其与 CD45 的结合，从而抑制 T 细胞凋亡。此外，RNA-seq 分析揭示了 LLS30 的一种新作用机制，将其肿瘤内在致癌作用与抗肿瘤免疫联系起来。这些发现表明，肿瘤来源的 Gal-1 通过诱导效应 T 细胞凋亡，有助于 PCa 中的免疫抑制 TME。使用 LLS30 靶向 Gal-1 可能提供增强抗肿瘤免疫力和改善免疫治疗的策略。版权所有 © 2024 Wang、Xia、Chang、Hsu、Wu、Chen 和 Shih。

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.Copyright © 2024 Wang, Xia, Chang, Hsu, Wu, Chen and Shih.