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Figure 5. Therapeutic concept and antitumor effects of CUR@PPC-aPD-1 in a B16F10 melanoma model. This figure illustrates CUR@PPC-aPD-1 as an aPD-1-targeted, dual pH-sensitive nanodrug designed to enhance antitumor immunity by combining nanocarrier-mediated drug delivery with immune checkpoint blockade. It conceptually shows how this platform may help overcome PD-1/PD-L1-mediated immunosuppression and improve therapeutic responsiveness within the TME. Model: B16F10 melanoma. Key readouts: PD-1⁺ T-cell tumor infiltration, CD8⁺ IFN-γ⁺ T-cell activation, IFN-γ and TNF-α production, expression of tumoricidal cytokines, tumor growth inhibition, and survival benefit. (A) Immunofluorescence imaging of B16F10 tumors, showing the effect of aPD-1 delivery on tumor infiltration by PD-1⁺ T cells; (B) Flow cytometric analysis of CD8⁺ IFN-γ⁺ T cells, showing that intracellular IFN-γ expression increased in the CUR@PPC and PPC-aPD-1 groups compared with the PBS group, with the highest proportion of IFN-γ-expressing cells observed in the CUR@PPC-aPD-1 group; (C) ELISA analysis of IFN-γ and TNF-α, showing that CUR@PPC-aPD-1 treatment yielded the highest levels of both cytokines; (D) Immunohistochemical staining of tumoricidal cytokines, including IFN-γ, TNF-α, and granzyme B, in B16F10 tumors, showing the strongest upregulation in the CUR@PPC-aPD-1 group; granzyme B is a cytotoxic effector molecule that induces DNA fragmentation; (E and F) Tumor growth and cumulative survival of mice receiving different treatments, showing that CUR@PPC-aPD-1 markedly inhibited tumor growth and significantly improved survival. Data are presented as mean ± SD. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001. Reprinted with permission from American Association for the Advancement of Science under a CC BY - NC 4.0 license^[70]. CUR: Curcumin; PPC: PDPA-PEG-CDM; PD-1: programmed cell death protein 1; PD-L1: programmed death-ligand 1; TME: tumor microenvironment; IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α; PBS: phosphate-buffered saline; ELISA: enzyme-linked immunosorbent assay.