Extended Data Fig. 5: Identification of potential factors driving mitochondrial dysfunction in CD8+ T cells.
From: Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion
a, GSEA of indicated signatures from the ranked list of genes differentially expressed in MDR/MGhi CD8+ TILs versus MDR/MGlo CD8+ TILs from YUMM1.7-OVA tumors. b, c, Hypoxia-related signaling in non-exhausted (non-Ex.), progenitor exhausted (Prog. Ex.), partially exhausted (Part. Ex.) and terminally exhausted (Term. Ex.) CD8+ T cells were examined by scRNA-seq analyses on melanoma samples collected from indicated references (b, non-Ex.: n = 253; Prog. Ex.: n = 42; Part. Ex.: n = 135; Term. Ex.: n = 135; c, non-Ex.: n = 441; Prog. Ex.: n = 63; Part. Ex.: n = 198; Term. Ex.: n = 198). d, e, The representative flow plots of mitophagy events (d) and MDR/MGlo population (e) in in vitro-activated OT-I Mito-QC and OT-I CD8+ T cells, respectively, cultured under indicated conditions. f, MDR/MGlo populations in in vitro-activated CD8+ T cells were determined by flow cytometry at indicated time points, followed by the quantifications of the percentage of MDR/MGlo population (n = 3 per group). g, MDR/MGlo populations in in vitro-activated CD8+ T cells treated with or without 50 μM MitoTempo was examined using flow cytometry (n = 3 per group). h, MDR/MGlo populations in in vitro-activated CD8+ T cells treated with indicated compounds were determined by flow cytometry. (O, oligomycin A; A, antimycin A) (n = 12 per group). i, j, MDR/MGlo populations in human in vitro-activated CD8+ T cells cultured either with indicated compounds (i) or under TCM/TCR/Hypoxia condition with or without the supplementation of 10 mM glucose (j) were determined by flow cytometry (n = 9 per group). Box plots display the data distribution though the quartiles with median in the centre and whiskers, which indicates 10 and 90 percentiles. Data are mean ± s.d. and were analyzed by two-tailed, unpaired Student’s t-test (f-j). Data are representative of two independent experiments with similar results (f and g) or are cumulative results from at least three independent experiments (h-j).
