Functional and metabolic features of CD8⁺ T cells are restored in patients with MM in remission but not in patients with relapsed MM. (A-B) Proportion of (A) CD8⁺ and (B) CD4⁺ T cells within BM mononuclear cells from patients with relapsed MM (n = 14) and patients with MM in remission (n = 12), the red line indicates controls (n = 10). (C-D) Proportions of NV, CM, EM, and EMRA (C) CD8⁺ and (D) CD4⁺ T cells in indicated BM samples. (E-F) Percentage of PD-1⁻TIGIT⁻, PD-1⁺TIGIT⁻, PD-1⁻TIGIT⁺, and PD-1⁺TIGIT⁺ (E) CD8⁺ and (F) CD4⁺ T cells in BM mononuclear cells from indicated samples. (G-H) Proportion of (G) CD8⁺ and (H) CD4⁺ T cells within BM mononuclear cells from each group expressing IFN-γ, TNF-α, IL-2, all 3 of these cytokines (multifunctional), or granzyme B after 4 hours of stimulation via CD3/CD28 Brefeldin A. (I) Correlation of percentage of malignant plasma cells within the BM sample with frequency of cells positive (+) for the indicated cytokines for samples combined for patients with MM at diagnosis (n = 12), patients with relapsed MM (n = 14), and patients with MM in remission (n = 12). (J) C₁₆-BODIPY uptake and (K) mitochondrial mass of BM and PB CD8⁺ T cells within each group as indicated. The red line indicates the mean value in patients with MM at diagnosis. For panels A-B,G-H,J-K (circles), significance was calculated using unpaired t test; for panel I, Pearson correlation; and 2-way ANOVA and Sidak multiple comparison tests for panel J; ∗P < .05 and ∗∗P < .01.