Lymphoma Gal-1 expression in the local microenvironment confers CD20 mAb resistance in vivo. (A-B) Gal-1 expression blocks CD20-mediated lymphoma clearance in vivo. Mice given BL3750^Ctrl or BL3750^Gal-1 cells were treated with control (open shapes) or CD20 (closed shapes) mAb 1 day later. Lymphoma volume (2 experiments, top panels) and mouse survival (2-3 experiments, n = 4-10 mice per group, bottom panels) were monitored for 60 days post-mAb treatment. (B) Representative lymphomas (top panel) and serum Gal-1 (lower panel) was measured in naïve mice and littermates given lymphoma cells 45 days after CD20 mAb treatment (2-3 experiments, 10 mice per group). (C) Human LGALS1 expression (GSE2350) by naïve, centroblast (CB), centrocyte (CC), and memory B-cell samples (open circles) in comparison with cells (closed circles) from patients with Burkitt lymphoma (BL), CLL [blood cells (1) or blood CD19⁺ cells (2)], diffuse large B-cell lymphoma [DBCL; lymph node biopsy (1) or node biopsy CD19⁺ cells (2)], follicular lymphoma (FL), hairy cell leukemia (HCL), or mantle cell lymphoma (MCL). (E-I) Significant differences between sample means are indicated. *P ≤ .05; **P ≤ .01; ***P ≤ .001.