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Immune Regulation and the Role of Extracellular Vesicles in Non-Small Cell Lung Cancer: Biological Mechanisms and
Nicole Ferrario1, Orazio Fortunato1, Patrizia Ghidotti1
1Unit of Epigenomics and Biomarkers of Solid Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
Abstract:
Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) representing the most common subtype. Despite major advances in immunotherapy, only a subset of patients benefits from current treatments, highlighting the need to better understand the tumor immune microenvironment (TIME) and the mechanisms underlying immune escape. In this context, extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in lung cancer. This review summarizes the current knowledge on the role of EVs in NSCLC progression and immune regulation. We discuss how EVs contribute to primary tumor growth, dissemination, and pre-metastatic niche formation through the transfer of proteins, metabolites and nucleic acids. Particular attention is given to EV-mediated modulation of immune cells, highlighting their role in both immune suppression and immune activation. Furthermore, we provide an overview of the emerging therapeutic applications of EVs in lung cancer, including their use as drug-delivery systems and immunotherapeutic platforms.
Insights
Extracellular vesicles (EVs) are crucial for non-small cell lung cancer (NSCLC) progression and immune evasion. This review explores their role in tumor growth, metastasis, and immune modulation, plus therapeutic potential.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
- Current immunotherapies benefit only a subset of NSCLC patients, necessitating a deeper understanding of the tumor immune microenvironment (TIME).
- Extracellular vesicles (EVs) are increasingly recognized as key mediators of intercellular communication in cancer.
Purpose of the Study:
- To review the current understanding of extracellular vesicle (EV) roles in NSCLC progression and immune regulation.
- To elucidate how EVs facilitate tumor growth, dissemination, and pre-metastatic niche formation.
- To summarize the therapeutic potential of EVs in NSCLC treatment.
Main Methods:
- Literature review of studies on extracellular vesicles in non-small cell lung cancer.
- Analysis of EV-mediated intercellular communication mechanisms.
- Evaluation of EV functions in immune modulation and therapeutic applications.
Main Results:
- EVs transfer proteins, metabolites, and nucleic acids, promoting NSCLC growth, spread, and pre-metastatic niche formation.
- EVs significantly modulate immune cells, contributing to both immune suppression and activation within the TIME.
- Emerging evidence supports the use of EVs as drug-delivery systems and immunotherapeutic agents for NSCLC.
Conclusions:
- Extracellular vesicles play a multifaceted role in NSCLC pathogenesis and immune evasion.
- Targeting EV-mediated communication presents a promising strategy for novel NSCLC therapies.
- Further research into EV biology and therapeutic applications is crucial for advancing NSCLC treatment.
