Fig. 7. RP-182 increases antitumor activity of CD8⁺ T cells and inhibits tumor growth in CD206^high patient-derived pancreatic cancer xenografts.

(A) Quantification of enzyme-linked immune absorbent spots (ELISpots) (IFN-γ-secreting CD8⁺ T cells of added total CD8⁺ T cells) after coculture of KP16 (left) and KPC cancer cells (right) and CD8⁺ T cells isolated from tumors and spleens. (B) Kaplan-Meier analysis of KP16 mice treated with anti-CD8 neutralizing antibody, anti-IgG₂ isotype control, and indicated combinations. (C) Quantification of flow cytometry analysis of CD45⁻CK19⁺ cancer cells expressing PD-L1 (left) and PD-1 expression on CD45⁺CD3e⁺CD8⁺ T cells (right) in KP16 tumors. (D) Best objective response (BOR) of KP16 tumors treated with vehicle (gray bars), anti-PD-L1 injections (purple), RP-182 (red), and anti-PD-L1 in combination with RP-182; n ≥ 7 animals per group. E. Tumor growth of CT-26 allografts, tumor weights at study endpoint shown on right. (F) Tumor growth of murine B16 melanoma. (G) Pancreatic cancer patient-derived xenotransplantation models that are CD206^high (#133R, #328R) or CD206^low (#295R, #057R) treated with RP-182, RP-426, or vehicle control; n ≥ 7 per group. (H) RP-182 administration rescues mice with chemically induced pulmonary fibrosis. Quantification of total body weights (in grams; top) and Kaplan-Meier survival analysis, error bars indicate SDs. (I) Pulmonary inflammatory infiltrates after bleomycin instillation. Images of H&E stains, quantification of measured weights of excised lungs on right; n = 4 per group. Scale bars, 50 μm. (J) Images of Masson’s trichrome staining, quantification of percent fibrosis positive area of 100 mm² examined lung surface on right. Scale bars, 50 μm. (K) Reduction of CD206-positive alveolar cell infiltrate in RP-182-treated mice. Immunofluorescence lung field images of noninstilled and bleomycin-instilled mice treated with vehicle or RP-182 stained with DAPI and anti-CD206 (green). Scale bars, 100 μm. Red arrows in insets indicate CD206-positive cells. Quantification of number of CD206-positive cells shown on right, n = 4 per group.