Figure 4.

Immune biomarkers associated with response. A, Shannon entropy of CR (n = 12) and NR (n = 11) pretreatment PB TCR samples. Uncorrected P = 0.15 comparing CR versus NR patients. TRB, TCR Vβ. B, Heatmap showing the 0 to 1 scaled mean fluorescence intensity values of 12 markers over the eight CD8⁺ BM subsets from all samples (NR: n = 11; CR: n = 8). The median marker expression identifies the markers that characterize each cell subset. Each CD8⁺ subpopulation is colored according to the cluster identified using the FlowSOM algorithm:

CD8 activated effector: DNAM1⁺CD28⁺KLRG1⁺CD69⁺CD56⁺; CD8 partially senescent: CD28⁺CD27⁺KRLG1⁺CD57⁺; CD8 progenitor exhausted: CD28⁺PD1⁺TIGIT⁺; CD8 TEMRA CD57⁻: CD45RA⁺KLRG1⁺CD57⁻; CD8 senescent: CD45RA⁺KLRG1⁺CD57⁺; CD8 DNAM1⁺CD28⁺: DNAM1⁺CD28⁺; CD8 DNAM1⁺PD1⁺: DNAM1⁺PD1⁺; and CD8 naïve: CCR7⁺CD45RA⁺CD27⁺CD28⁺. C, UMAP visualization overlaid with contour plots (kernel density estimation) of the eight CD8⁺ BM subpopulations in nonresponders (NR, n = 11) and those achieving complete remission (CR, n = 8), at baseline (base_CR, base_NR) or after therapy (post_CR, post_NR). Each CD8⁺ subpopulation is colored according to the cluster identified using the FlowSOM algorithm. D, Boxplots showing the relative abundance of BM CD8⁺ subpopulations in NR and CR patients at baseline and posttreatment. Horizontal bars indicate median values. Asterisks indicate adjusted P values (*, P_adj < 0.05). E, Frequency of BM CD8⁺CD45RA⁻CD27⁺/intCD28⁺PD1⁺TCF1⁺ T cells in patients who achieved CR compared with NRs at baseline and at response assessment (*, P < 0.05). Tpex, precursor exhausted.