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Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2020 May; Vol. 69 (5), pp. 813-824. Date of Electronic Publication: 2020 Feb 13. - Publication Year :
- 2020
-
Abstract
- Despite significant therapeutic improvements chronic lymphocytic leukemia (CLL) remains an incurable disease and there is a persistent pursuit of new treatment alternatives. Lurbinectedin, a selective inhibitor of active transcription of protein-coding genes, is currently in phase II/III clinical trials for solid tumors such as small-cell lung cancer (SCLC). In this study, we aimed to evaluate the activity of Lurbinectedin on circulating mononuclear cells from CLL patients and to determine whether Lurbinectedin could affect the cross-talk between B-CLL cells and the tumor microenvironment. We found that Lurbinectedin induced a dose- and time-dependent death in all cell types evaluated, with B cells, monocytes and monocytic myeloid derived suppressor cells (Mo-MDSC) being the most susceptible populations. At sub-apoptotic doses, Lurbinectedin decreased the expression of CCR7 in B-CLL cells and impaired their migration towards CCL19 and CCL21. Furthermore, 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 leukemic cells in combination with its effects on the tumor microenvironment. Our findings encourage further investigation of Lurbinectedin as a potential therapy for CLL.
- Subjects :
- Apoptosis drug effects
Apoptosis immunology
B-Lymphocytes drug effects
B-Lymphocytes immunology
B-Lymphocytes metabolism
Cell Survival drug effects
Cell Survival immunology
Chemokine CCL19 immunology
Chemokine CCL19 metabolism
Chemokine CCL21 immunology
Chemokine CCL21 metabolism
Drug Screening Assays, Antitumor
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic immunology
Humans
Leukemia, Lymphocytic, Chronic, B-Cell blood
Leukemia, Lymphocytic, Chronic, B-Cell immunology
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Monocytes drug effects
Monocytes immunology
Monocytes metabolism
Myeloid-Derived Suppressor Cells drug effects
Myeloid-Derived Suppressor Cells immunology
Myeloid-Derived Suppressor Cells metabolism
Primary Cell Culture
Receptors, CCR7 immunology
Receptors, CCR7 metabolism
Tumor Cells, Cultured
Tumor Microenvironment immunology
Carbolines pharmacology
Heterocyclic Compounds, 4 or More Rings pharmacology
Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Tumor Microenvironment drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 69
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 32055920
- Full Text :
- https://doi.org/10.1007/s00262-020-02513-y