肺癌在全球仍然是引发癌症相关死亡的主要原因，尽管在诊断和治疗方面取得了进展，但生存率仍然很低。肺癌的进展是一个多方面的动态现象，涵盖了癌细胞及其微环境（包括免疫细胞）之间的相互作用。外泌体是由许多细胞在正常和应激情况下释放的小型膜包囊，用于细胞之间的通讯。肿瘤源外泌体（TEXs）具有多样的新抗原和载体，如蛋白质、RNA和DNA，并具有反映肿瘤遗传复杂性的独特分子组成。TEXs含有免疫抑制和免疫刺激因子，可能通过影响固有和适应性免疫组分而在免疫调节中发挥作用。此外，它们传递的信号有助于促进肺癌的转移、上皮间充质转化（EMT）、血管生成和免疫抑制。这使得它们成为研究肿瘤免疫环境的有价值资源，有望为肺癌的预后、诊断和免疫治疗开发非侵入性生物标志物铺平道路。尽管免疫检查点抑制剂（ICI）免疫治疗在治疗初期癌症方面显示出有希望的结果，但大多数患者最终会出现适应性耐药。新兴证据表明，TEXs可能作为免疫治疗反应的预后生物标志物，并对系统免疫抑制和肿瘤进展产生重要影响。因此，了解TEXs及其在肺癌肿瘤发生和对免疫治疗的反应中的作用是一个令人激动的研究领域，并需要进一步的调查。本综述强调了TEXs作为肺癌进展的重要贡献者及其在肺癌免疫-oncology中的临床意义，包括其可能用作监测疾病进展和预后的生物标志物，以及使用外泌体作为改善肺癌治疗靶标的新证据。© 2023. 意大利国立癌症研究所"Regina Elena"。

Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.© 2023. Italian National Cancer Institute ‘Regina Elena’.