Effects of idelalisib, a PI3Kδ inhibitor used on in the treatment of Chronic Lymphocytic Leukemia (CLL), on macrophages and its interactions with other therapeutic agents.

COLADO ANA; SARAPURA MARTÍNEZ VALERIA; FERNANDEZ GRECCO HORACIO; GIORDANO MIRTA; ELÍAS ESTEBAN; CORDINI, GREGORIO; BEZARES FERNANDO; GAMBERALE ROMINA; AMONDARAIN MIKELE; VERGARA-RUBIO, MARICEF; VEREERTBRUGGHEN ALEXIA; MORANDE PABLO; BORGE MERCEDES

Tucumán

Congreso; LXVII Reunión Científica Anual de la Sociedad Argentina de Inmunología.; 2019

Sociedad Argentina de Inmunología

B-cell receptor signaling inhibitors (BCRi) have changed the treatment-paradigm in CLL. Some BCRi were successfully used to overcome leukemic-cell resistance to venetoclax, a Bcl-2 inhibitor recently incorporated in CLL-treatment. On the other hand, some BCRi affect innate-immune cells, which might increase susceptibility to infections. Here we evaluated the effect of idelalisib, a BCRi that targets PI3Kδ, on i) macrophage-phenotype and cytokine secretion, and ii) the resistance of leukemic cells to venetoclax induced by activated T-cells.Human monocytes were cultured with GM-CSF+IFN-ɣ or M-CSF+IL-10 to obtain M1 or M2 macrophages respectively. Immobilized anti-CD3 was used to activate T-cells. M1/M2-associated markers, cell-viability and leukemic and T-cell activation were evaluated by flow cytometry, and TNF-α by ELISA. We found that idelalisib did not affect the expression of CD206, CD163 (M2-markers) and CD86 (M1-marker), as reported with other BTKi (n=6), while it impaired TNF-α secretion induced by LPS without affecting macrophage viability (n=8, p