Abstract：
Exosomes are the primary category of extracellular vesicles (EVs), which are lipid-bilayer vesicles with biological activity spontaneously secreted from either normal or tansformed cells. They serve a crucial role for intercellular communication and affect extracellular environment and the immune system. Tumor-derived exosomes (TEXs) enclose high levels of immunosuppressive proteins, including programmed death-ligand 1 (PD-L1). PD-L1 and its receptor PD-1 act as crucial immune checkpoint molecules, thus facilitating tumor advancement by inhibiting immune responses. PDL-1 is abundantly present on tumor cells and interacts with PD-1 on activated T cells, resulting in T cell suppression and allowing immune evasion of cancer cells. Various FDA-approved monoclonal antibodies inhibiting the PD-1/PD-L1 interaction are commonly used to treat a diverse range of tumors. Although the achieved results are significant, some individuals have a poor reaction to PD-1/PD-L1 blocking. PD-L1-enriched TEXs may mimic the impact of cell-surface PD-L1, consequently potentiating tumor resistance to PD1/PD-L1 based therapy. In light of this, a strong correlation between circulating exosomal PD-L1 levels and response rate to anti-PD-1/PD-L1 antibody treatment has been evinced. This article inspects the function of exosomal PDL-1 in developing resistance to anti-PD-1/PD-L1 therapy for opening new avenues for overcoming tumor resistance to such modalities and development of more favored combination therapy.
摘要：
外泌体是细胞外囊泡（EV）的主要类别，它们是从正常或tansformed细胞自发分泌的具有生物活性的脂双层囊泡。它们在细胞间通讯中起着至关重要的作用，并影响细胞外环境和免疫系统。肿瘤来源的外泌体（TEX）包含高水平的免疫抑制蛋白，包括程序性死亡配体1（PD-L1）。PD-L1及其受体PD-1作为重要的免疫检查点分子，从而通过抑制免疫反应促进肿瘤进展。PDL-1大量存在于肿瘤细胞上，并与活化T细胞上的PD-1相互作用，导致T细胞抑制并允许癌细胞的免疫逃避。各种FDA批准的抑制PD-1/PD-L1相互作用的单克隆抗体通常用于治疗不同范围的肿瘤。虽然取得的成果是显著的,一些个体对PD-1/PD-L1阻断反应较差.富含PD-L1的TEX可以模拟细胞表面PD-L1的影响，从而增强肿瘤对基于PD1/PD-L1的治疗的抗性。鉴于此,循环外泌体PD-L1水平与抗PD-1/PD-L1抗体治疗的应答率之间有很强的相关性.本文研究了外泌体PDL-1在对抗PD-1/PD-L1治疗产生耐药性方面的功能，为克服肿瘤对此类方式的耐药性和开发更受欢迎的联合治疗开辟了新的途径。
