Extended Data Fig. 8: Murine TFR cells are depleted by anti-CTLA-4 thereapy.
From: Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
a,b, Foxp3YFPcre/YFPcre Bcl6fl/fl (TFR knockout) mice or Foxp3YFPcre/YFPcre Bcl6+/+ control mice were s.c. inoculated with B16F10-OVA cells and treated with isotype control or anti-PD-1 Abs at indicated time points, frequency and Ki-67 expression of CD8+ T cells and CD4+ T cells in tumor-draining lymph nodes of mice treated as indicated in, n = 7 mice for ctrl+isotype ctrl, n = 6 mice for ctrl+anti-PD-1, n = 9 mice for the two TFR ko groups. c, Mice were s.c. inoculated with B16F10-OVA or MC38-OVA cells and treated with anti-CTLA-4 Abs at day 10 and day 13. Flow-cytometric analysis of the frequency of tumor-infiltrating TREG and TFR cells, as well as fold depletion of both cell types following anti-CTLA-4 therapy in the B16F10-OVA model (left panel, n = 9 mice, P = 0.0435) and MC38-OVA model (right panel, n = 5 mice, P = 0.0079). d, Survival curves of an independent cohort of melanoma patients (n = 29) stratified into TFRhi (>5.075% of CD4+ cells co-expressing FOXP3 and BCL-6) and TFRlo (<5.075% of cells co-expressing FOXP3 and BCL-6) e, IHC analysis of the frequency of FOXP3+BCL6+ TFR cells with a cutoff (orange line) set to upper limit of normal of 5.075% pertaining to (Extended Data Fig. 8d), P = 0.0654. f, Survival curves of melanoma patients stratified into CXCR5hi (frequency of CXCR5 + cells >8.336%) and CXCR5lo (frequency of CXCR5 + cells <8.336%). g, IHC analysis of the frequency of CXCR5 + cells with a cutoff (orange line) set to upper limit of normal of 8.375% pertaining to (Extended Data Fig. 8f), P = 0.0002. Data are mean + /− s.e.m., Significance for comparisons were computed using two-tailed Mann–Whitney test (c,e,g) or Mantel–Cox test (d,f). Data in (a–c) are representative of two independent experiments.
