Amato Luisa, De Rosa Caterina, De Rosa Viviana, Heydari Sheikhhossein Hamid, Ariano Annalisa, Franco Paola, Nele Valeria, Capaldo Sara, Di Guida Gaetano, Sepe Filippo, Di Liello Alessandra, De Rosa Giuseppe, Tuccillo Concetta, Gambardella Antonio, Ciardiello Fortunato, Morgillo Floriana, Tirino Virginia, Della Corte Carminia Maria, Iommelli Francesca, Vicidomini Giovanni
Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy.
Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy.
Cancers (Basel). 2024 Sep 14;16(18):3151. doi: 10.3390/cancers16183151.
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（SCLC）是一种具有高度侵袭性且增殖迅速的肺癌亚型。大多数患者对铂类化疗和PD-1/PDL-1抑制剂联合治疗反应良好。不幸的是，并非所有患者都能从这种治疗方案中获益，且几乎没有其他替代疗法。在这种情况下，识别新的生物标志物和差异化治疗策略以改善肿瘤反应变得迫在眉睫。在此，我们研究了小细胞肺癌患者外周血单个核细胞（PBMCs）释放的外泌体（EXs）在介导免疫系统与肿瘤对治疗反应中的功能相互作用中的作用。在本研究中，我们发现，对化学免疫疗法有不同反应的小细胞肺癌患者的PBMC-EXs显示出不同水平的免疫（STING和MAVS）和上皮-间质转化（EMT）（Snail和c-Myc）标志物。我们证明，与非反应者（NR）小细胞肺癌患者来源的PBMC-EXs相比，最佳反应者（BR）患者来源的PBMC-EXs在体外能够显著诱导小细胞肺癌细胞系凋亡增加。PBMC-EXs能够影响细胞活力并调节凋亡标志物、DNA损伤和复制应激途径，以及EMT的发生。我们的工作提供了概念验证，即PBMC-EXs可作为研究癌细胞与免疫细胞之间相互作用的工具，且PBMC-EXs在体外具有促进癌细胞死亡和降低肿瘤侵袭性的能力。
