Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia

RISNIK, DENISE; COLADO, ANA; PODAZA, ENRIQUE; ALMEJÚN, MARÍA BELÉN; ELÍAS, ESTEBAN ENRIQUE; BEZARES, RAIMUNDO FERNANDO; FERNÁNDEZ-GRECCO, HORACIO; SEIJA, NOÉ; OPPEZZO, PABLO; BORGE, MERCEDES; GAMBERALE, ROMINA; GIORDANO, MIRTA

CANCER IMMUNOLOGY IMMUNOTHERAPY

SPRINGER

Año: 2020 vol. 69 p. 813 - 824

0340-7004

Chronic lymphocytic leukemia (CLL) is still an incurable disease and there is an active pursuit of new treatment alternatives. Lurbinectedin is a selective inhibitor of active transcription of protein-coding genes and is currently in phase II/III clinical trials for solid tumors such as small-cell lung cancer (SCLC). Our main goal was to evaluate the activity of Lurbinectedin on circulating mononuclear cells from CLL patients and to determine whether Lurbinectedin could affect the cross-talk of B-CLL cells with the tumor microenvironment. We found that Lurbinectedin induced a dose- and time-dependent death of all cell types evaluated, being B cells, monocytes and monocytic myeloid derived suppressor cells (Mo-MDSC) the most susceptible populations. At sub-apoptotic doses, Lurbinectedin decreased the expression of CCR7 on B-CLL cells and impaired their migration towards CCL19 and CCL21. In addition, low concentrations of Lurbinectedin stimulated the synthesis of pro-IL1β in monocytes and nurse-like cells, without inducing the inflammasome activation. Altogether, these results indicate that Lurbinectedin might have antitumor activity in CLL due to its direct action on the leukemic cells in combination with its effects on the tumor microenvironment. Our findings encourage further investigation of Lurbinectedin as a potential therapy for CLL.