Exosome-mediated crosstalk between immune cells and tumor microenvironment in lung cancer: Implications for immune evasion and therapeutic resistance.

Lung cancer (LC), a leading cause of cancer-related mortality globally, relies on intricate crosstalk within the tumor microenvironment (TME) to drive immune evasion and therapeutic resistance. Exosomes serve as key mediators of intercellular communication within the TME. They regulate molecular signaling between tumor cells and their microenvironment in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Exosomes carry a variety of bioactive substances. These substances work together to impair the immune system, speed up the growth of tumors, encourage invasion and metastasis, and exacerbate therapeutic resistance. Tumor-derived exosomes (TEXs) facilitate immune evasion by impairing cytotoxic T lymphocytes (CTLs) function, promoting regulatory T cells (Tregs) differentiation, and polarizing macrophages toward the tumor-supportive M2 phenotype. Exosomes also make cells more resistant to chemotherapy, targeted treatment, and immunotherapy by changing the way cells send signals, changing the TME to help cells stay alive, and sending proteins that make cells more resistant. Due to their stability and detectability in bodily fluids, exosomes represent promising noninvasive biomarkers for LC diagnosis, prognosis, and treatment monitoring. Translational strategies targeting exosome biogenesis, release, or uptake, as well as modified exosomes for targeted drug delivery and immune modulation, hold potential to overcome treatment resistance and improve clinical outcomes. This review summarizes the core mechanisms of exosome-mediated immune evasion and therapeutic resistance in LC, and highlights their key translational implications for clinical application.