Journal: Cell Reports Medicine

Article Title: Fc-optimized anti-CTLA-4 antibodies increase tumor-associated high endothelial venules and sensitize refractory tumors to PD-1 blockade

doi: 10.1016/j.xcrm.2025.102141

Figure Lengend Snippet: Fc-enhanced mouse anti-CTLA-4 antibodies prune TA-HEVs in the absence of concurrent PD-1 blockade (A) Treatment schedule. i.p., intraperitoneal; control, isotype control antibodies. (B and C) Mean and individual tumor growth. Data were obtained from two independent experiments ( n = 10 mice per group). (D–G) Frequency of FOXP3 + Tregs in tumor, numbers of tumor-infiltrating FOXP3 + Tregs and FOXP3 − Tconv, and ratio of Tconv to Treg cell numbers in tumors following indicated treatments. Each symbol represents an individual mouse ( n = 10, two independent experiments). (H–M) Frequencies of CD45 − CD31 high endothelial cells, TA-HECs, MECA-79 + CD62P + TA-HECs, numbers of TA-ECs and TA-HECs, and mean fluorescence intensity (MFI) of MECA-79 and CD62P in TA-HECs, following indicated treatments, quantified by flow cytometry. Each symbol represents an individual mouse ( n = 10, two independent experiments). (N) Histograms showing expression of PD-L1 in CD45 − CD31 high tumor endothelial cells following indicated treatments, quantified by flow cytometry. MFI of PD-L1 is quantified. Each symbol represents an individual mouse ( n = 4–5). (O) Treatment schedule. i.p., intraperitoneal; control, isotype control antibodies. (P and Q) Mean and individual tumor growth. Data were obtained from two independent experiments (control, n = 8 mice; 9D9-IgG2a + anti-PD-1, n = 10 mice). (R–T) Numbers of tumor-infiltrating FOXP3 + Tregs and FOXP3 − Tconv, and ratio of Tconv to Tregs cell numbers in tumors following indicated treatments. Each symbol represents an individual mouse ( n = 8–10, two independent experiments). (U) Frequency of TA-HECs. Representative dot plots of TA-HECs are shown. Each symbol represents an individual mouse ( n = 8–10, two independent experiments). Data are shown as mean ± SEM. All p values were determined by unpaired two-tailed Student’s t test except for graph in (N) for which p values were determined by one-way ANOVA with Tukey’s multiple comparison test, and for (B) and (P) for which p values were determined by two-way ANOVA. See also .

Article Snippet: RecombiMAb Mouse IgG1 anti-Mouse CTLA-4 (clone 9H10-CP146) , Bio X Cell , Cat# CP146; RRID: AB_2927521.

Techniques: Control, Fluorescence, Flow Cytometry, Expressing, Two Tailed Test, Comparison