Tumor microenvironment-driven resistance to immunotherapy in non-small cell lung cancer: strategies for Cold-to-Hot tumor transformation

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Non-small cell lung cancer (NSCLC) represents a formidable challenge in oncology due to its molecular heterogeneity and the dynamic suppressive nature of tumor microenvironment (TME). Despite transformative impact immune checkpoint inhibitors (ICIs) on therapy, majority NSCLC patients experience resistance, necessitating novel approaches overcome evasion. This review highlights shared subtype-specific mechanisms resistance within TME, including metabolic reprogramming, dysfunction, physical barriers. Beyond well-characterized components such as regulatory T cells, tumor-associated macrophages, myeloid-derived suppressor emerging players - neutrophil extracellular traps, tertiary lymphoid structures, exosomal signaling networks underscore TME's complexity adaptability. A multi-dimensional framework is proposed transform cold, immune-excluded tumors into hot, immune-reactive ones. Key strategies include enhancing infiltration, modulating immunosuppressive networks, activating dormant pathways. Cutting-edge technologies, single-cell sequencing, spatial transcriptomics, nanomedicine, are identified pivotal tools for decoding TME personalizing therapeutic interventions. By bridging mechanistic insights with translational innovations, this advocates integrative that combine ICIs modulators, vascular normalizers, therapies STING agonists vaccines. The synergistic potential these poised achieve durable antitumor immunity. Ultimately, vision underscores importance interdisciplinary collaboration real-time profiling refining precision NSCLC, offering blueprint extending advances other malignancies.

Language: Английский

Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 14 - 14

Published: Dec. 27, 2024

Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) great successes delivering mRNAs. After an mRNA-LNP vaccine enters a cell via endosome, mRNA is translated into antigen, which can activate adaptive immunity. mRNAs bind to various pattern recognition receptors (PRRs), including toll-like (TLRs), increase production inflammatory cytokines. This review summarizes mechanisms innate immunity induced by Polyethylene glycol (PEG) has been employed as component vaccine. PEGylated display enhanced stability preventing aggregation particles. However, PEGylation cause adverse reactions, blood clearance (ABC) complement activation anaphylaxis. Mechanisms PEG-induced ABC phenomenon anaphylaxis are presented discussed. There studies aimed at reducing immune responses associated with PEG make safe effective vaccines. Effects modifying or replacing also Modifying induce tolerance, prevent hypersensitivity reactions Current tolerance induction association summarized. might be helpful for developing

Language: Английский