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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2947-2958
Number of pages12
JournalClinical Cancer Research
Issue number10
Publication statusPublished - 2021 May

Bibliographical note

Funding Information:
This study was supported by a National Research Foundation grant and funded by the Ministry of Science and ICT, Republic of Korea (NRF-2020R1C1C1010618) to H. Cho.

Publisher Copyright:
© 2021 American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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