Extended Data Fig. 6: Stem-like CD4 T cells are the source of Th1 cells in response to Treg depletion and aCTLA4 therapy.
From: Differentiation fate of a stem-like CD4 T cell controls immunity to cancer
a-b) Phenotypic analysis of recovered stem and Treg SMARTAs in TDLNs (a) and tumors (b) 7 days after transfer in WT or Treg depleted (DTR) recipients for each condition. Medians are represented in each summary graph and analyzed by Kruskal-Wallis test with Dunn’s multiple-comparison tests. Data are representative of 2 independent experiments (n = 13 for stem-like and n = 5 for Tregs). c) Representative FOXP3 and CTLA4 staining with accompanying CTLA4 geometric MFI in TDLNs and tumors in TRAMPC1-GP bearing mice. Medians are shown and analyzed by two sided unpaired Mann-Whitney U test (n = 10 mice). d) Experimental design to test how Tregs suppress stem-like differentiation through CTLA4 in TRAMPC1-GP bearing mice. e) Tumor kinetics shown as mean tumor diameter ± s.d. in untreated (n = 9), aCTLA4 4F10 (n = 9), or aCTLA4 9H10 (n = 9) mice and analyzed by Kruskal-Wallis test with Dunn’s multiple-comparison tests. f-g) Representative f) GP66 staining and g) phenotype of tumor specific CD4 T cells in TDLNs in each treatment group. h) Phenotype of bulk PD1 + CD4 T cells for each treatment group in tumors. Medians are represented in each summary graph and were analyzed by Kruskal-Wallis test with Dunn’s multiple-comparisons tests (n = 9 for each group). i) Experimental design to test the effects of aCTLA4 therapy in orthotopic RENCA-HA-Luciferase mice. j) Phenotype analysis of bulk PD1 + CD4 T cells in the tumor for untreated or 9H10 CTLA4 treated orthotopic RENCA-HA-Luc mice. Medians are shown and were analyzed by two sided unpaired Mann-Whitney U test (n = 9 for Untx and n = 5 for 9H10 aCTLA4 group).
