Extended Data Fig. 6: Immunological characterization of genetically heterogeneous mouse and human multiple myeloma.

a) MM with lower frequency of immune cells was more common in patients older than 70 years. Fisher’s exact test. b) Measurement of the tumor mutation burden in MM samples from mice (n = 23) and patients (n = 24) according to whole-exome sequencing (WES) studies of somatic mutations. Pearson correlation studies of the TMB quantified and the T and NK cells infiltrating the BM in mouse MM (c) and human MM (d); MGUS and SMM cases were not included in these correlations. e) Comparison of the BM immune phenotypes including the number of activated PD-1⁺, TIGIT⁺, and LAG3⁺ CD8⁺ T lymphocytes at MM stages in MI_cγ1 (n = 13) vs. BI_cγ1 (n = 13) mice (complementary to Fig. 5c). f) Comparison of the number of PD-1⁺ Treg cells in the BM of MI_cγ1 (n = 3) mice and in BI_cγ1 (n = 5) mice (complementary to Fig. 5c). g-h) Kaplan-Meier survival curves in MI_cγ1 mice and BI_cγ1 mice undergoing depletion of CD4⁺ and CD8⁺ T cells. Monoclonal antibodies were administered by i.p. injection when MI_cγ1 and BI_cγ1 mice were 4.5 and 6 months of age, respectively. Mice received 100 µg of anti-CD4, anti-CD8, or rat IgG control antibodies, administered on days +1, +4, and +8 and then weekly for 8 weeks. Median overall survival, mOS. The number of mice included on each cohort is represented. i) Pharmacological inhibition of MYC repressed Cd274/PD-L1 expression at transcriptional and protein levels in the MM2732 cell line established from the Trp53-MI_cγ1 model. Mean and s.d. of 2-4 independent experiments are shown. Boxes represent median, upper and lower quartiles and whiskers represent minimum to maximum range (b, e and f). Two-tailed t test or Mann-Whitney test P values (b, e, f and i) are indicated. Log-rank (Mantel-Cox) test was used in g and h. *p < 0.05; **p < 0.01; NS, non-significant.