Figure 6. PPARγ-Deficient T Cells Show Improved Antitumor Potential.

(A–C) Three-day activated WT and PPARγ-deficient T cells were used to determine (A) cell surface expression of stem cell antigen (Sca1), CD122, and CD127; (B) ECAR time course in response to glucose, oligomycin, and 2DG; and (C) WT and PPARγ^−/− T cells were activated either in presence or absence orlistat (100 µM). OCR under basal condition and in response to indicated mitochondrial inhibitors was determined.

(D) WT and PPARγ^−/− T cells were activated either in presence or absence of orlistat (100 µM) and used to determine cell viability with 7AAD staining.

(E) Bodipy conjugated FL C₁₂ uptake; and expression of CD36 by flow cytometry in day 3 activated WT and PPARγ^−/− T cells.

(F) Day 3 activated WT and PPARγ-deficient T cells were cultured overnight ± oleate (30 µM), followed by 24 h of starvation in low glucose (2 mM) media, and then stained with Bodipy. The numerical values within the FACS overlay plots indicate MFI. Adjacent bar diagrams represent cumulative data from at least three repeat experiments.

(G) C57BL/6 HLA-A2⁺ mice (n = 12 mice/group) were inoculated (s.c.) with 0.3 × 10⁶ B16F10-A2⁺ melanoma cells for 9 days, after which mice either kept untreated or adoptively transferred with melanoma reactive 1 × 10⁶ TIL1383I tyrosinase epitope-reactive TCR transduced T cells generated using splenocytes from WT or PPARγ^creCD4^flox mice. Tumor growth was measured using digital calipers twice weekly. Left: estimated growth curves for each experimental condition. Right: survival curve (p value WT versus PPARγ^−/−: 2e–04). (A–G) Error bars represent mean ± SD. *p < 0.05, **p < 0.01.

See also Figure S6.