Fig. 4: Depleting the tumor microenvironment of BCL-X_L leads to an apoptosis-induced decrease in the number of TI-Tregs.

a Percentage of Tregs following treatment with the BCL-X_L targeting PROTAC DT2216 (or vehicle) in the draining lymph nodes (DLN), spleens, and tumors from MC38 tumor-bearing mice. b Amount of pan-caspase labeling in TI-Tregs from MC38 tumor-bearing mice following treatment with DT2216 (or vehicle) as assessed by flow cytometry. MFI of pan-caspase activation probe is shown. c–e Percentages of Tconv (c) and CD8⁺ T (e) cells following treatment with DT2216, and d amount of caspase labeling in TI-Tconv cells. f Representative histogram showing levels of granzyme B (Gzmb) in TI-CD8⁺ T cells from MC38 tumor-bearing mice treated with DT2216 (or vehicle). g Number of perforin⁺, granzyme B (Gzmb)⁺, or Ki-67⁺ TI-CD8⁺ T cells from MC38 tumor-bearing mice following treatment with DT2216 (or vehicle); a, c, e, and g: n = 5 biological replicates for DLN and tumors, n = 4 biological replicates in control, and n = 5 in DT2216 group for spleen; b and d: n = 4 biological replicates in control and n = 5 in DT2216 group. h, i Ratios of TI-Treg/TI-Tconv or TI-Treg/TI-CD8⁺ T cells in (h, n = 3 biological replicates) human breast cancer slice sections or (i, n = 3 biological replicates) in human colon cancer slices, after ex vivo treatment with DT2216 (25 nM, or vehicle). Shown are the mean ± s.d. Two-sided unpaired t test was performed, with P values indicated.