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Figure 1. Immunotherapy and signaling pathways in melanoma. Tumor antigen processing and presentation to T cells is shown. Ipilimumab blocks CTLA-4 and B7 interaction, leading to increased immune response against tumors. PD-1 and PD-L1 inhibitors function by blocking PD-1/PD-L1 interaction, creating a cascade of immune responses that helps kill malignant cells. TIM-3 and LAG-3 are checkpoint proteins that play a role in modulating response to immunotherapy and suppressing anti-cancer immunity. Relatlimab represents a pioneering human IgG4 monoclonal blocking antibody that targets LAG-3. The PI3K-AKT-mTOR pathway is negatively regulated by PTEN in the cytoplasm. PTEN loss leads to an increase in MDSCs, T_reg cells, IDO1, and PD-L1 expression. IFN-γ induces PD-L1 in cancer cells through the JAK-STAT-IRF-1 pathway, as shown. LAG-3: Lymphocyte-activation gene 3; PD-1: programmed cell death protein 1; PD-L1/2: programmed cell death ligand 1 and 2; CLTA-4: cytotoxic T-lymphocyte-associated protein 4; STAT: signal transducer and activator of transcription; T_reg: regulatory T; MDSCs: myeloid-derived suppressor cells; APC: antigen-presenting cell; TCR: T cell receptor; IRF-1: interferon regulatory factor-1; TIM-3: T cell immunoglobulin and mucin domain 3; IFN-γ: interferon-gamma; IDO: indoleamine 2,3-dioxygenase; PTEN: phosphatase and tensin homolog; PI3K: phosphatidylinositol-3-kinase; AKT: protein kinase B; mTOR: mammalian target of rapamycin; Gal9: galectin 9.