Extended Data Fig. 3: TRAP1 deletion in macrophages advances immune evasion.
From: Cancer suppresses mitochondrial chaperone activity in macrophages to drive immune evasion
(a) Schematic of the experimental design for YUMM1.7 tumor inoculation. Trap1+/+ x Rag1−/− and Trap1−/− x Rag1−/− mice were administered i.p. with anti-NK1.1 antibody followed by subcutaneous injection 5 × 105 YUMM1.7 cells. (b-f) Tumor growth (b), tumor weight (c), representative tumor image (d), and frequency of CD206+ TAMs (e) and ARG1+ TAMs (f) from Trap1+/+ x Rag1−/− and Trap1−/− x Rag1−/− tumor-bearing mice on day 16 (n = 4 mice per group). Data are representative of two independent experiments. (g-o) Wild-type mice were injected subcutaneously with B16-F10 cells together with either Trap1+/+ or Trap1−/− BMDMs, or Trap1−/−BMDMs overexpressing TRAP1 (Trap1O/E). Tumor growth (g) and tumor weight (h) from mice given the indicated treatment. Absolute number of TAMs (i), frequencies of CD206+ TAMs (j) and ARG1+ TAMs (k), absolute number of TILs (l), frequencies of IFNγ+ CD8 (m), IFNγ+ CD4 (n) and FoxP3+ CD4 (o) T cells (n = 5 mice per group). Data are representative of two independent experiments. (p) Frequencies of TAMs, TILs, total DCs, DC1s, DC2s, neutrophils, monocytes, NKs in Trap1wt and Trap1cKO tumor-bearing mice on day 16 (n = 5 mice per group). Data are representative of two independent experiments. (q, r) Tumor growth (q) and tumor weight (r) in Trap1wt and Trap1cKO mice subcutaneously injected with 5 × 105 Lewis lung carcinoma (LLC) cells. Tumors were harvested on day 16 post-tumor transplantation (n = 4 mice per group). Each symbol represents one individual. Data are representative of two independent experiments. (s) Proliferation of CTV-labeled CD8+ T cells activated with anti-CD3 and anti-CD28, and co-cultured with Trap1+/+ or Trap1−/− BMDMs treated with YUMM1.7 TCM or LPS+IFNγ (M1) at a 1:10 ratio for 72 h (n = 4). Data are representative of two independent experiments. All data are mean ± s.e.m. and were analyzed using a two-tailed, unpaired Student’s t-test (c, e, f, p, r), a one-way ANOVA with Sidak’s multiple comparison test (h-o, s) or a two-way ANOVA with Tukey’s multiple comparison test (b, g, q).
