[Galectin-3 in the Lung Cancer Microenvironment: Immunomodulation and Therapeutic Breakthroughs].

Abstract

Lung cancer remains one of the most prevalent and deadly malignancies worldwide, with persistently low five-year survival rates. This poor prognosis is primarily attributed to challenges such as difficulties in early diagnosis, high tumor heterogeneity, and strong therapeutic resistance. Although recent advances in targeted therapies and immune checkpoint inhibitors have significantly improved the prognosis of some patients, the majority still encounter primary or secondary resistance. Galectin-3, a multifunctional glycan-binding protein, is constitutively expressed in pulmonary tissues. Its expression encompasses bronchial and alveolar epithelial cells, the pulmonary vasculature, and resident immune cells. Galectin-3 plays a central role in lung cancer progression by regulating tumor cell proliferation, immune evasion, and angiogenesis. The complex immunosuppressive mechanisms within the tumor microenvironment not only facilitate tumor growth and metastasis but also partially limit the efficacy of cancer immunotherapies. Overcoming these barriers requires the exploration of novel regulatory targets to break through therapeutic bottlenecks. This review systematically elucidates the mechanisms by which galectin-3 interacts with immune cells (e.g., T cells, macrophages) in the tumor microenvironment and evaluates its potential as a therapeutic target, including inhibitor development and combination immunotherapy strategies. The findings aim to provide a theoretical foundation for advancing galectin-3 as a novel therapeutic target in lung cancer and offer new perspectives for overcoming current immunotherapy resistance.
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