免疫检查点阻断（ICB）疗法在各种癌症类型中取得了广泛的适用性和持久的临床反应。然而，总体反应率仍然不理想，因为一些患者没有反应或产生耐药性。由于抗原呈递不足而导致肿瘤微环境中 CD8 细胞毒性 T 细胞 (CTL) 的低浸润与 ICB 的先天耐药性密切相关。细胞表面主要组织相容性复合物 I 类 (MHC-I) 表达的持续时间和空间分布对于内源性肿瘤抗原的有效呈递以及随后被 CTL 识别和清除至关重要。肿瘤细胞通过多种机制减少 MHC-I 的表面表达，从而损害抗原呈递途径并逃避免疫和/或对 ICB 治疗产生耐药性。随着越来越多的研究关注肿瘤细胞膜MHC-I的运输和降解，这可能会影响肿瘤免疫治疗的有效性。有必要总结膜MHC-I易位到细胞质并通过溶酶体降解的调节机制。我们回顾了内体-溶酶体 MHC-I 转运的最新进展，并强调了肿瘤细胞逃避 CTL 检测和清除的手段。我们还总结了针对这些途径的新治疗策略，以增强经典 ICB 治疗，并为优化癌症免疫治疗提供新途径。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Immune checkpoint blockade (ICB) therapy has achieved broad applicability and durable clinical responses across cancer types. However, the overall response rate remains suboptimal because some patients do not respond or develop drug resistance. The low infiltration of CD8+ cytotoxic T cells (CTLs) in the tumor microenvironment due to insufficient antigen presentation is closely related to the innate resistance to ICB. The duration and spatial distribution of major histocompatibility complex class I (MHC-I) expression on the cell surface is critical for the efficient presentation of endogenous tumor antigens and subsequent recognition and clearance by CTLs. Tumor cells reduce the surface expression of MHC-I via multiple mechanisms to impair antigen presentation pathways and evade immunity and/or develop resistance to ICB therapy. As an increasing number of studies have focused on membrane MHC-I trafficking and degradation in tumor cells, which may impact the effectiveness of tumor immunotherapy. It is necessary to summarize the mechanism regulating membrane MHC-I translocation into the cytoplasm and degradation via the lysosome. We reviewed recent advances in the understanding of endosomal-lysosomal MHC-I transport and highlighted the means exploited by tumor cells to evade detection and clearance by CTLs. We also summarized new therapeutic strategies targeting these pathways to enhance classical ICB treatment and provide new avenues for optimizing cancer immunotherapy.Copyright © 2024 Elsevier B.V. All rights reserved.