大量临床前研究证明了T细胞免疫球蛋白粘蛋白结构域蛋白3（Tim-3）作为抑制性受体对T细胞的抑制功能，从而导致了抗Tim-3阻断抗体的临床开发。然而，最近的研究表明，Tim-3不仅在T细胞上表达，还在肿瘤微环境（TME）中的多种细胞类型上表达，包括树突状细胞（DC）、自然杀伤（NK）细胞、巨噬细胞和肿瘤细胞。因此，免疫微环境中Tim-3的阻断不仅影响T细胞的功能，还会影响其他细胞的功能。例如，Tim-3阻断可以增强DC调节先天免疫和适应性免疫的能力。 Tim-3 阻断在 NK 细胞功能中的作用存在争议，因为它在某些情况下可以增强 NK 细胞的抗肿瘤功能，而在其他情况下则产生相反的效果。此外，Tim-3 阻断可以促进巨噬细胞极化从 M2 表型逆转为 M1 表型。此外，Tim-3阻断可以通过抑制肿瘤细胞的增殖和转移来抑制肿瘤的发展。总之，越来越多的证据表明，其他细胞类型中的 Tim-3 在抗 Tim-3 疗法的疗效中也发挥着关键作用。了解抗 Tim-3 疗法在非 T 细胞中的功能有助于阐明临床患者中观察到的不同反应，从而更好地制定相关治疗策略。本综述旨在讨论 Tim-3 在 TME 中的作用，并强调 Tim-3 阻断对 T 细胞以外的肿瘤免疫微环境的影响。版权所有 © 2024。由 Elsevier Ltd 出版。

Numerous preclinical studies have demonstrated the inhibitory function of T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) on T cells as an inhibitory receptor, leading to the clinical development of anti-Tim-3 blocking antibodies. However, recent studies have shown that Tim-3 is expressed not only on T cells but also on multiple cell types in the tumor microenvironment (TME), including dendritic cells (DCs), natural killer (NK) cells, macrophages, and tumor cells. Therefore, Tim-3 blockade in the immune microenvironment not only affect the function of T cells but also influence the functions of other cells. For example, Tim-3 blockade can enhance the ability of DCs to regulate innate and adaptive immunity. The role of Tim-3 blockade in NK cells function is controversial, as it can enhance the antitumor function of NK cells under certain conditions while having the opposite effect in other situations. Additionally, Tim-3 blockade can promote the reversal of macrophage polarization from the M2 phenotype to the M1 phenotype. Furthermore, Tim-3 blockade can inhibit tumor development by suppressing the proliferation and metastasis of tumor cells. In summary, increasing evidence has shown that Tim-3 in other cell types also plays a critical role in the efficacy of anti-Tim-3 therapy. Understanding the function of anti-Tim-3 therapy in non-T cells can help elucidate the diverse responses observed in clinical patients, leading to better development of relevant therapeutic strategies. This review aims to discuss the role of Tim-3 in the TME and emphasize the impact of Tim-3 blockade in the tumor immune microenvironment beyond T cells.Copyright © 2024. Published by Elsevier Ltd.