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Adaptive Natural Killer Cells Facilitate Effector Functions of Daratumumab in Multiple Myeloma

 Hyunsoo Cho  ;  Kyung Hwan Kim  ;  Hoyoung Lee  ;  Chang Gon Kim  ;  Haerim Chung  ;  Yoon Seok Choi  ;  Su-Hyung Park  ;  June-Won Cheong  ;  Yoo Hong Min  ;  Eui-Cheol Shin  ;  Jin Seok Kim 
 CLINICAL CANCER RESEARCH, Vol.27(10) : 2947-2958, 2021-05 
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Purpose: To investigate the different roles of heterogeneous natural killer (NK)-cell subpopulations in multiple myeloma and to identify NK-cell subsets that support the robust anti-myeloma activity of daratumumab via antibody-dependent cellular cytotoxicity (ADCC).

Experimental design: We performed single-cell RNA sequencing of NK cells from patients with newly diagnosed multiple myeloma (NDMM) and delineated adaptive NK cells in their bone marrow (BM). We further characterized the distinct immunophenotypic features and functions of adaptive NK cells by multicolor flow cytometry in 157 patients with NDMM.

Results: Adaptive NK cells exhibit a significantly lower level of CD38 expression compared with conventional NK cells, suggesting that they may evade daratumumab-induced fratricide. Moreover, adaptive NK cells exert robust daratumumab-mediated effector functions ex vivo, including cytokine production and degranulation, compared with conventional NK cells. The composition of adaptive NK cells in BM determines the daratumumab-mediated ex vivo functional activity of BM NK cells in patients with NDMM. Unlike conventional NK cells, sorted adaptive NK cells from the BM of patients with NDMM exert substantial cytotoxic activity against myeloma cells in the presence of daratumumab.

Conclusions: Our findings indicate that adaptive NK cells are an important mediator of ADCC in multiple myeloma and support direct future efforts to better predict and improve the treatment outcome of daratumumab by selectively employing adaptive NK cells.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
Kim, Chang Gon(김창곤)
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Chung, Hae Rim(정해림) ORCID logo https://orcid.org/0000-0002-7926-9285
Cho, Hyunsoo(조현수) ORCID logo https://orcid.org/0000-0003-2651-6403
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