Fig. 4: mtDNA mutation and cytoLbNOX-associated microenvironment remodeling sensitizes tumors to checkpoint blockade.
a, Schematic of the experimental plan and dosing regimen for B78-D14 tumors with anti-PD1 monoclonal antibody (mAb). b, Representative images of isolated tumors at day 21. c, Tumor weights at day 21 (n = 15, 19, 12 and 10 individual tumors). d, Schematic of experimental plan and dosing regimen for Hcmel12 tumors with anti-PD1, anti-PD-L1 or anti-CTLA4 mAbs. e, Representative images of collected tumors at day 13 for each drug regimen. f, Tumor weights at day 13 (n = 11, 11, 12 and 10 anti-PD1, n = 12 anti-PD-L1 and n = 12 anti-CTLA4 individual tumors) for each drug regimen. g, Schematic of the experimental plan and dosing regimen for 4434 tumors with anti-PD1 mAb. h, Representative images of treated tumors at day 20 and untreated tumors at endpoint. i, Tumor weights at day 21 (n = 13 individual tumors). j, Stratification of a metastatic melanoma patient cohort by mtDNA status. k, Response rate of patients to nivolumab by tumor mtDNA mutation status. P values were determined using one-way ANOVA with Sidak multiple comparisons test (c,f), one-tailed Student’s t-test (i) or chi-squared test (k). Error bars, s.d. Measure of centrality is mean. Number of replicates are described across conditions from left to right as presented.
