Small cell lung cancer (SCLC) is a highly invasive and rapidly proliferating lung tumor subtype. Most patients respond well to a combination of platinum-based chemotherapy and PD-1/PDL-1 inhibitors. Unfortunately, not all patients benefit from this treatment regimen, and few alternative therapies are available. In this scenario, the identification of new biomarkers and differential therapeutic strategies to improve tumor response becomes urgent. Here, we investigated the role of exosomes (EXs) released from the peripheral blood mononuclear cells (PBMCs) of SCLC patients in mediating the functional crosstalk between the immune system and tumors in response to treatments. In this study, we showed that PBMC-EXs from SCLC patients with different responses to chemoimmunotherapy showed different levels of immune (STING and MAVS) and EMT (Snail and c-Myc) markers. We demonstrated that PBMC-EXs derived from best responder (BR) patients were able to induce a significant increase in apoptosis in SCLC cell lines in vitro compared to PBMC-EXs derived from non-responder (NR) SCLC patients. PBMC-EXs were able to affect cell viability and modulate apoptotic markers, DNA damage and the replication stress pathway, as well as the occurrence of EMT. Our work provides proof of concept that PBMC-EXs can be used as a tool to study the crosstalk between cancer cells and immune cells and that PBMC-EXs exhibit an in vitro ability to promote cancer cell death and reduce tumor aggressiveness.
小细胞肺癌是一种侵袭性强、增殖迅速的肺部肿瘤亚型。多数患者对铂类化疗联合PD-1/PDL-1抑制剂的治疗方案反应良好。然而并非所有患者都能从该方案中获益，且替代治疗方案极为有限。在此背景下，寻找新的生物标志物和差异化治疗策略以改善肿瘤反应显得尤为迫切。本研究探讨了小细胞肺癌患者外周血单个核细胞释放的外泌体在介导免疫系统与肿瘤之间功能性交互作用中的角色。研究发现，对化学免疫治疗反应不同的患者，其外周血单个核细胞来源外泌体中免疫标志物（STING和MAVS）及上皮间质转化标志物（Snail和c-Myc）的表达水平存在差异。实验证明，与无应答患者相比，最佳应答患者的外周血单个核细胞来源外泌体在体外能显著诱导小细胞肺癌细胞系凋亡增加。这些外泌体能够影响细胞活力，调节凋亡标志物、DNA损伤及复制应激通路，并调控上皮间质转化的发生。本研究从概念上证实：外周血单个核细胞来源外泌体可作为研究癌细胞与免疫细胞交互作用的工具，并在体外展现出促进癌细胞死亡、降低肿瘤侵袭性的能力。
肿瘤(癌症)患者之家