Shugan-Liangxue Prescription Inhibits Immune Escape Against Breast Cancer by Regulating Tryptophan Metabolism.

ObjectiveTryptophan metabolism plays a pivotal role in promoting tumor progression by modulating immune escape in breast cancer (BC). Shugan-Liangxue prescription (SLP), a traditional Chinese medicine, has shown beneficial effects in enhancing antitumor immunity for BC treatment. This study aims to investigate the effect of SLP on tryptophan metabolism in BC and to explore the underlying mechanisms.MethodsThe immunopharmacological BC model in rats was established by chemical carcinogen induction and complete freund's adjuvant perturbations and treated with SLP. Tamoxifen and other metabolism-associated drugs were used as controls. The therapeutic efficacy of SLP was evaluated by tumor volume, weight, and oncocyte proliferation. Serum cytokines and subsets of immune cells in the spleen were measured to evaluate the anti-tumor immunity. Metabolite levels and expressions of signal molecules of tryptophan metabolic pathway were measured to explore the mechanisms.ResultsOur findings demonstrated that SLP treatment significantly inhibited tumor growth and tumor cell proliferation, and enhanced antitumor immunity by promoting Th1 polarization, increasing cytotoxic immune cells (CD8+ T cells, NKG2D+ NK cells), and reducing inhibitory immune cells (Foxp3+ Tregs, NKG2A+ NK cells, M2 macrophages) in the spleen. Additionally, SLP regulated glucose and lipid metabolism, as evidenced by reduced serum glucose and non-esterified fatty acid levels. SLP suppressed tryptophan catabolism by down-regulating expression of IDO1 and AhR and reducing kynurenine levels.ConclusionsIn summary, correlative analyses suggest SLP may mitigate breast cancer immune escape partially via the Trp metabolic pathway to boost anti-tumor immune surveillance, and its immunomodulatory activity is potentially linked to glucose and lipid reprogramming. While our findings support the involvement of the Trp-Kyn-AhR axis, causal verification via pathway rescue and inhibition assays is still needed.