High Expression of the Costimulatory Checkpoint Factor DNAM-1 by CD4 + T-Cells from Multiple Myeloma Patients Refractory to Daratumumab-Containing Regimens.

Autor: Iversen KF; Institute of Regional Health Science, University of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark. katrine.fladeland.iversen@rsyd.dk.; Section of Hematology, Department of Internal Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark. katrine.fladeland.iversen@rsyd.dk., Nederby L; Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark., Lund T; Department of Hematology, Odense University Hospital, J.B. Winsløvs Vej 4, 5000, Odense C, Denmark., Plesner T; Institute of Regional Health Science, University of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark.; Section of Hematology, Department of Internal Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark.
Jazyk: angličtina
Zdroj: Clinical hematology international [Clin Hematol Int] 2022 Sep; Vol. 4 (3), pp. 107-116. Date of Electronic Publication: 2022 Aug 09.
DOI: 10.1007/s44228-022-00013-7
Abstrakt: Multiple myeloma is an incurable disease characterized by unregulated growth of malignant plasma cells in the bone marrow (BM). Tumor-induced dysfunction of T-cells may be responsible for immune evasion and failure of immunotherapy. Therefore, a better understanding of the phenotype of T-cells at the tumor site is needed. We assessed the expression of immune regulatory receptors on T-cell subsets from peripheral blood (PB) and BM using multicolor flow cytometry. Paired PB and BM samples were collected from newly diagnosed, treatment-naïve myeloma patients (n = 19) and patients progressing during treatment with the CD38 monoclonal antibody daratumumab alone or in combination with other anti-myeloma drugs (n = 39). We observed that CD4 + T-cells from both PB and BM of patients relapsing on daratumumab have a higher expression of the costimulatory checkpoint receptor DNAM-1. The potential role of DNAM-1 + CD4 + T-cells in the development of resistance to daratumumab needs further exploration. We also observed that the inhibitory checkpoint receptor TIGIT is more frequently expressed by BM CD8 + T-cells from myeloma patients than PD-1 and CTLA-4, which supports the hypothesis that TIGIT may play a central role in the immune escape of the malignant plasma cells.
(© 2022. The Author(s).)
Databáze: MEDLINE
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