Immunoregulatory Role of Extracellular Vesicles in Advanced Non-Small Cell Lung Cancer
Abstract
The treatment of advanced non-small cell lung cancer (NSCLC) has greatly improved in the last decade thanks to the introduction into clinical practice of immune checkpoint blockers (ICBs), alone or in combination with chemotherapy. Despite these huge advantages, a portion of patients do not experience a benefit from ICBs. Tumor PD-L1, the only clinical available biomarker for ICB, showed limited predictive value since even low PD-L1 patients could benefit from ICB treatment. The research of a more robust and reliable biomarker represents a huge clinical need. Extracellular vesicles (EVs) for their intrinsic properties could be exploited as circulating biomarkers and considering their role in intercellular communication, they may play a role in influencing the immune response during ICB. In this thesis, EVs were investigated as possible alternative biomarkers to predict the response to ICB, used in combination with chemotherapy, in advanced stage NSCLC patients with low tumor PD-L1 levels. Furthermore, we investigated the potential immune regulatory properties of patient-derived EVs in this therapeutic setting. Starting from the comprehensive characterization of plasma EVs, we found differences in terms of both surface marker composition and microRNAs cargo in EVs isolated from Responder, Stable Disease, and Non-Responder patients. In particular, we identified 5 EV-associated features (miR-142-3p, let-7a-5p, % CD11b+, % CD63+CD11b+, %CD63+EpCAM+) that correlated with…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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