非小细胞肺癌（NSCLC）是致癌死亡的主要原因。肿瘤发展取决于癌细胞与肿瘤微环境的相互作用。在这里，我们发现来自NSCLC患者的肿瘤中有端粒酶催化亚基TERT的拷贝数和mRNA表达量增加，导致更低的生存率。此外，在TCGA队列的NSCLC患者中，TERT的表达主要与CD8+ T淋巴细胞浸润减少以及髓系来源的免疫抑制细胞的浸润增加有关。我们还展示了在小鼠中通过6-硫基-DG处理诱导的TERT缺陷和功能障碍性端粒体降低了肺肿瘤的植入和血管生成，增加了DNA损伤反应、细胞周期阻滞和凋亡，同时也减少了增殖、炎症、肺肿瘤免疫抑制和侵袭，这些都是在引起刘易斯肺癌时的。此外，6-硫基-DG处理的人类NSCLC移植瘤表现出增加的端粒体损伤、细胞周期阻滞和凋亡，以及减少的增殖，导致肿瘤生长减缓。我们的结果表明，靶向端粒体可能是治疗NSCLC的有效策略。©2023.作者。

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death. Tumor progression depends on interactions of cancer cells with the tumor microenvironment. Here, we find increased copy number and mRNA expression of the catalytic subunit of telomerase, TERT, in tumors from NSCLC patients, contributing to a lower survival. Moreover, TERT expression in NSCLC patients from the TCGA cohort is mainly associated to the reduced infiltration of CD8+ T lymphocytes, as well as to increased infiltration of myeloid-derived suppressor cells (MDSCs). We also show that TERT deficiency and dysfunctional telomeres induced by 6-thio-dG treatment in mice reduced lung tumor implantation and vascularization, increased DNA damage response, cell cycle arrest and apoptosis, as well as reduced proliferation, inflammation, lung tumor immunosupression and invasion upon induction of a Lewis lung carcinoma (LLC). Furthermore, 6-thio-dG-treated human NSCLC xenografts exhibited increased telomere damage, cell cycle arrest and apoptosis, as well as reduced proliferation, resulting in a reduced tumor growth. Our results show that targeting telomeres might be an effective therapeutic strategy in NSCLC.© 2023. The Author(s).