Extracellular Vesicles in Non-Small-Cell Lung Cancer: Functional Role and Involvement in Resistance to Targeted Treatment and Immunotherapy

Abstract

Targeted and immunological therapies have become the gold standard for a large portion of non-small cell lung cancer (NSCLC) patients by improving significantly clinical prognosis. However, resistance mechanisms inevitably develop after a first response, and almost all patients undergo progression. The knowledge of such a resistance mechanism is crucial to improving the efficacy of therapies. So far, monitoring therapy responses through liquid biopsy has been carried out mainly in terms of circulating tumor (ctDNA) analysis. However, other particles of tumor origin, such as extracellular vehicles (EVs) represent an emerging tool for the studying and monitoring of resistance mechanisms. EVs are now considered to be ubiquitous mediators of cell-to-cell communication, allowing cells to exchange biologically active cargoes that vary in response to the microenvironment and include proteins, metabolites, RNA species, and nucleic acids. Novel findings on the biogenesis and fate of these vesicles reveal their fundamental role in cancer progression, with foreseeable and not-far-to-come clinical applications in NSCLC.

Role of extracellular vesicles in chronic lung disease

“…[119][120][121] Explorative approaches for integrating liquid biopsy into managing common cancer types have been developed, including 32 studies focusing on EVs. 122 Here, we concentrate on EV studies that identified biomarkers between control and disease states and targets contributing to lung cancer progression.…”

Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy—The Role of Liquid Biopsy in Unraveling the Puzzle

“…They can also induce apoptosis (or suppression) of immune cells such as CD8+ T cells. Hence, TEX influence the sensitivity of tumor cells to immunotherapy [ 25 , 67 , 71 ].…”

Cell-derived vesicles for delivery of cancer immunotherapy

“…EVs can be roughly divided into three types: micro-vesicles, apoptotic bodies, and exosomes [48,49]. Among them, the diameter of exosomes is about 30-150 nm, which can transfer RNA, functional proteins, lipids and metabolites to recipient cells in the body, and actively participate in the communication between the host and pathogen cells and organs [50][51][52]. Most cells can secrete and ingest exosomes.…”