【Cell】以色列学者发文：揭示免疫逃逸新机制并提出增强肿瘤免疫力的治疗途径

Core Insights - The study published in the journal "Cell" reveals that melanoma cells secrete large extracellular vesicles (melanosomes) that express major histocompatibility complex (MHC) molecules, which stimulate CD8+ T cells through T cell receptors (TCR), leading to T cell dysfunction and apoptosis [3] Group 1: Immune Evasion Mechanism - Melanoma cells utilize MHC export to protect themselves from cytotoxic T cell attacks, revealing a novel immune evasion mechanism [3][7] - The research indicates that melanosomes carry tumor-associated antigens with higher affinity and immunogenicity, competing directly with TCR-MHC interactions [3] Group 2: Impact of Inhibiting Melanosome Secretion - Inhibition of melanosome secretion significantly reduces tumor immune evasion, enhancing the effectiveness of CD8+ T cells in the tumor microenvironment [3][7] - The use of the depigmenting agent kojic acid, which blocks melanin production, resulted in decreased melanosome secretion without affecting melanoma proliferation or MHC I expression [4][5] Group 3: Experimental Findings - In mouse models, the inhibition of melanosome secretion led to increased infiltration of CD8+ T cells into the tumor microenvironment and slowed tumor growth [5][7] - The study demonstrates that blocking melanosome secretion can enhance the activity and effectiveness of tumor-infiltrating CD8+ T cells [7]