This research explores the paradoxical relationship between glucose restriction and cancer metastasis, specifically focusing on lung metastasis. The study reveals that while low-carbohydrate diets or impaired glucose metabolism can suppress primary tumor growth, they unexpectedly promote lung metastasis by altering the immune landscape. This occurs through exosomes containing TRAIL protein, which are released by glucose-deprived cancer cells. These exosomes then polarize lung macrophages, leading to the exhaustion of natural killer (NK) cells via the PVR-TIGIT pathway, thereby creating an environment conducive to tumor colonization. The research also highlights plasma exosomal TRAIL as a superior biomarker for predicting early postoperative lung metastasis in hepatocellular carcinoma (HCC) patients, offering potential for improved diagnostic and therapeutic strategies like anti-TIGIT therapy.

References:

• Wu C Y, Huang C X, Lao X M, et al. Glucose restriction shapes pre-metastatic innate immune landscapes in the lung through exosomal TRAIL[J]. Cell, 2025.