In vivo avadomide-based therapy effect on immune activation in peripheral blood and tumor biopsies. Immunophenotyping flow cytometric measurements for ICOS, PD-1, and PD-L1-positive (A) CD8⁺ T cells and (B) CD4⁺ T cells from the peripheral blood of CLL patients (n = 7-9) treated with avadomide and obinutuzumab therapy. Cycle 2, day 15, and cycle 3, day 8 data are compared with baseline (screening blood samples analysis). (C) Representative cropped medial optical section confocal images of CD8⁺ T-cell conjugates with autologous CLL tumor cells (blue) showing increased ICOS (green) at F-actin (red) immune synapses with avadomide treatment. Original magnification, ×63 (scale bars: 10 μm). (D) RNA-seq was performed on paired lymph node tissue biopsies from 18 R/R DLBCL patients at screening (baseline) and following avadomide therapy (on-treatment, cycle 1, day 10/15) (clinical trial: NCT01421524). The heatmap shows the relative expression and significant enrichment (P < .05) of chemokine signaling pathway genes (KEGG_CHEMOKINE_SIGNALING_PATHWAY) following avadomide therapy in DLBCL.