Department of Surgery, Trauma and Vascular Surgery Clinical Research, Hamad General Hospital, 3050, Doha, Qatar.
Faculty of Medical Sciences, Ala-Too International University, Bishkek, Kyrgyzstan.
J Exp Clin Cancer Res. 2023 Aug 29;42(1):221. doi: 10.1186/s13046-023-02753-7.
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.
肺癌仍然是全球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,包括癌细胞及其微环境之间的相互作用,其中包括免疫细胞。外泌体是由许多细胞类型在正常和应激情况下释放的小膜结合囊泡,以允许细胞之间的通讯。肿瘤衍生的外泌体(TEXs)具有多样化的新抗原和货物,如蛋白质、RNA 和 DNA,并且具有独特的分子组成,反映了肿瘤遗传的复杂性。TEXs 包含免疫抑制和免疫刺激因子,并可能通过影响先天和适应性免疫成分在免疫调节中发挥作用。此外,它们通过促进转移、上皮-间充质转化(EMT)、血管生成和免疫抑制来传递信号,从而促进肺癌的进展。这使它们成为研究肿瘤免疫环境的有价值资源,这可能为开发非侵入性生物标志物铺平道路,这些标志物可以帮助预测、诊断和治疗肺癌。虽然免疫检查点抑制剂(ICI)免疫疗法在治疗早期癌症方面显示出有希望的结果,但大多数患者最终会随着时间的推移产生适应性耐药。新出现的证据表明,TEXs 可以作为免疫治疗反应的预后生物标志物,对全身免疫抑制和肿瘤进展都有重大影响。因此,了解 TEXs 及其在肺癌发生和对免疫疗法的反应中的作用是一个令人兴奋的研究领域,需要进一步研究。本综述强调了 TEXs 作为肺癌进展的关键贡献者的作用及其在肺免疫肿瘤学中的临床意义,包括它们作为监测疾病进展和预后的生物标志物的可能用途,以及关于利用外泌体作为改善肺癌治疗的靶点的可能性的新出现证据。
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