利用免疫检查点阻断（ICB）治疗非小细胞肺癌（NSCLC）已取得巨大进展。针对肿瘤细胞上表达的程序性细胞死亡蛋白 1 (PD-1) 及其配体 PD-L1 的治疗已证明具有提高患者生存率的潜力。一个未解决的问题涉及肿瘤微环境 (TME) 内外泌体 PD-L1 诱导的免疫抑制，特别是 CD8 T 细胞。我们的研究揭示了 LAMTOR1 在抑制 PD-L1 外泌体和促进 NSCLC 中 CD8 T 细胞浸润方面的重要作用。通过与 HRS 的相互作用，LAMTOR1 促进 PD-L1 溶酶体降解，从而减少外泌体 PD-L1 的释放。值得注意的是，LAMTOR1 促进 PD-L1 溶酶体降解的能力依赖于特定的泛素化位点和 HRS 结合序列。研究结果表明，利用 LAMTOR1 构建肽可以作为增强 NSCLC 免疫疗法疗效的有前景的策略。 LAMTOR1 如何抑制外泌体 PD-L1 释放的发现和理解为改善免疫治疗的潜在治疗策略提供了见解。有必要开展进一步的研究和临床试验，以探讨靶向 LAMTOR1 治疗 NSCLC 的可行性和有效性。© 2024。作者。

Great progress has been made in utilizing immune checkpoint blockade (ICB) for the treatment of non-small-cell lung cancer (NSCLC). Therapies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, expressed on tumor cells, have demonstrated potential in improving patient survival rates. An unresolved issue involves immune suppression induced by exosomal PD-L1 within the tumor microenvironment (TME), particularly regarding CD8+ T cells. Our study unveiled the crucial involvement of LAMTOR1 in suppressing the exosomes of PD-L1 and promoting CD8+ T cell infiltration in NSCLC. Through its interaction with HRS, LAMTOR1 facilitates PD-L1 lysosomal degradation, thereby reducing exosomal PD-L1 release. Notably, the ability of LAMTOR1 to promote PD-L1 lysosomal degradation relies on a specific ubiquitination site and an HRS binding sequence. The findings suggest that employing LAMTOR1 to construct peptides could serve as a promising strategy for bolstering the efficacy of immunotherapy in NSCLC. The discovery and comprehension of how LAMTOR1 inhibits the release of exosomal PD-L1 offer insights into potential therapeutic strategies for improving immunotherapy. It is imperative to conduct further research and clinical trials to investigate the feasibility and efficacy of targeting LAMTOR1 in NSCLC treatment.© 2024. The Author(s).