胸腺五肽通过胸腺再生和 T 细胞功能重编程增强抗肿瘤免疫

Background/Objectives : T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5's antitumor efficacy and underlying immunological mechanisms. Methods : We evaluated TP5's therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma.

Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results : The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms.

Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus-tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion.

Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions : TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions.

Our findings provide compelling evidence for TP5's clinical translation in cancer treatment.