Fig. 4: Immune features of multiple myeloma progression.

a, Distribution of lymphoid cell subpopulations in the BM of mice with MGUS and MM, and in control mice. b, Two-tailed Pearson correlation analyses between the number of BM PCs in mice at MGUS and MM states with T cells or NK cells in the BM. c, Classification of MM samples into categories according to the abundance of T and NK lymphoid cells in the BM with respect to that in healthy mice. d, MM cases with higher number of infiltrating immune cells contained more tumor-reactive PD-1+CD8+ T cells and Treg cells. Two-tailed Pearson correlation analysis between CD8+ T cells and Treg cells in the BM (right). e, Characterization of the BM lymphoid cell composition by flow cytometry in BM samples from patients with MGUS, SMM and MM. f, Two-tailed Pearson correlation analyses between the percentage of PCs in the BM from MM patients and the percentage of T or NK cells in the BM. g, Classification of MM patients (n = 652) into those with lower and higher number of immune cells in the BM microenvironment with respect to healthy donors (HDs; n = 24). h, Tumors with high immune infiltrates contained more tumor-reactive PD-1+ CD8+ T cells and Treg cells in the BM compared with MM cases with a lower number of immune cells. Two-tailed Pearson correlation analysis between the percentages of CD8+ T cells in BM and the percentage of Treg cells (right). i, MM cases with more abundant immune cells had increased immunoglobulin secretion with respect to the remaining cases. j, Two-tailed Pearson correlation analyses between the T and NK lymphoid cell infiltrate in BM from mice (n = 59) and humans with MM (n = 638) and the age. k, Quantification of the BM lymphoid infiltrates including CD4+, CD8+ and NK cells across genetic subgroups of mouse and human MM. Boxes represent the median, upper and lower quartiles and whiskers represent minimum to maximum range (a, d, e, h, i and k). Kruskal–Wallis test P values adjusted for multiple comparisons by Dunn’s test (a, b and k) and Mann–Whitney test P values (d, h and i) are indicated. *P < 0.05; **P < 0.01; ***P < 0.001.