Lenalidomide repairs immune synapse on the long term. (A) List of canonical pathways related to cell motility and signal transduction upregulated in PD-1⁺ T cells. (B) Individual conjugates from mixed experiments using purified patient T cells (blue) with healthy allogeneic B cells (green) were selected at random for imaging and scored semi-quantitatively for accumulation of F-actin (red) at the immune synapse. Synapse score measured in an ex vivo immune synapse assay in 7 first-line patients (C) and in 2 R/R patients with FL (D). Each dot relates to a single immune synapse, and at least 50 T/B conjugates were scored for each sample. Median values are depicted as red lines; green rectangles indicate patients with no detectable circulating lymphoma cells; and orange rectangles highlight 2 patients presenting with leukemic-phase disease. D0, first day of the first cycle of treatment (before lenalidomide intake); D7, seventh day of the first cycle (before obinutuzumab infusion); D28, first day of the second cycle (before lenalidomide intake); end, end of induction. ***P < .001, Dunn multiple comparisons test.