Ahn Minseo, Mun Jeong-Geon, Han Yohan, Seo Jae Ho
Department of Biochemistry, Wonkwang University School of Medicine, Iksan, Republic of Korea.
Sarcopenia Total Solution Center, Wonkwang University School of Medicine, Iksan, Republic of Korea.
Front Immunol. 2025 Jun 12;16:1601266. doi: 10.3389/fimmu.2025.1601266. eCollection 2025.
Extracellular vesicles (EVs), including exosomes and microvesicles, play crucial roles in cancer progression by mediating the communication between cancer cells and their microenvironment. Cancer cell-derived EVs promote tumor growth, metastasis, and immune evasion by carrying bioactive materials, such as proteins, RNAs, DNA fragments, and lipids but, immunotherapy aims to enhance the immune response against cancer; however, resistance remains a major challenge. Cancer cell-derived EVs contribute to this resistance by delivering immunosuppressive molecules that impair T cell activation, promote the expansion of regulatory T cells (Tregs), and reduce natural killer (NK) cell cytotoxicity, thereby allowing cancer cells to evade immune surveillance. Additionally, cancer cell-derived EVs can carry immune checkpoint proteins, such as Programmed Death-Ligand 1 (PD-L1), which bind to the Programmed Death-1 (PD-1) receptor on T cells, leading to T cell exhaustion and reduced anti-tumor activity. This mechanism reflects how cancer cells directly evade immune detection and contributes to the overall resistance to immune checkpoint blockade therapies, such as anti-PD-1 or anti-PD-L1 antibodies. By delivering these immunomodulatory molecules, EVs not only contribute to local immune suppression but also create a systemic environment that is less favorable for effective anticancer immunity. Therefore, understanding the role of EVs in the immunotherapy resistance is crucial for developing targeted strategies to counteract their effects and ultimately improve therapeutic outcomes. Here we encourage researchers to pay more attention to the role of cancer cell-derived EVs in overcoming immunotherapeutic resistance, because such efforts may be one of the most promising approaches to address immunotherapy resistance in the future.
细胞外囊泡（EVs），包括外泌体和微囊泡，通过介导癌细胞与其微环境之间的通讯在癌症进展中发挥关键作用。癌细胞衍生的EVs通过携带生物活性物质（如蛋白质、RNA、DNA片段和脂质）促进肿瘤生长、转移和免疫逃逸，而免疫疗法旨在增强针对癌症的免疫反应；然而，耐药性仍然是一个主要挑战。癌细胞衍生的EVs通过传递损害T细胞活化、促进调节性T细胞（Tregs）扩增并降低自然杀伤（NK）细胞细胞毒性的免疫抑制分子来促成这种耐药性，从而使癌细胞逃避免疫监视。此外，癌细胞衍生的EVs可携带免疫检查点蛋白，如程序性死亡配体1（PD-L1），其与T细胞上的程序性死亡1（PD-1）受体结合，导致T细胞耗竭并降低抗肿瘤活性。这种机制反映了癌细胞如何直接逃避免疫检测，并导致对免疫检查点阻断疗法（如抗PD-1或抗PD-L1抗体）的整体耐药性。通过传递这些免疫调节分子，EVs不仅有助于局部免疫抑制，还会创造一个不利于有效抗癌免疫的全身环境。因此，了解EVs在免疫治疗耐药性中的作用对于制定针对性策略以抵消其影响并最终改善治疗结果至关重要。在此，我们鼓励研究人员更多地关注癌细胞衍生的EVs在克服免疫治疗耐药性中的作用，因为此类努力可能是未来解决免疫治疗耐药性最有前景的方法之一。
