Treatment significantly exacerbated these defects, as demonstrated by the weaker immune response in treated CLL participants compared to W&W participants: BTK inhibitors block critical B-cell receptor signaling needed for antibody generation, anti-CD20 antibodies deplete the very B cells required for humoral immunity, and BCL-2 inhibition can alter the metabolic fitness of both humoral and cellular immune compartments (40, 41). This evidence concerns the gene BCL2 and B-cell chronic lymphocytic leukemia.