Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma

Frontiers in Immunology
Sara TognarelliEvelyn Ullrich

Abstract

Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients, we were able to isolate autologous tumor cells, and we could demonstrate that IL-2/15 stimulated autologous NK cells were able to significantly improve their killing capacity of autologous tumor cells. With the aim to further improve the NK cell killing capacity against MM cells, we investigated the potential use of NK specific check point inhibitors with focus on NKG2A because this inhibitory NK cell receptor was upregulated following ex vivo cytokine stimulation and MM cells showed HLA-E expression that could even be increased by exposure...Continue Reading

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Citations

Feb 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qiuchen QiZhongxi Zhao
Jan 31, 2020·Frontiers in Microbiology·Joana R LériasMarkus Maeurer
Mar 11, 2020·Frontiers in Immunology·Aviad Ben-ShmuelMira Barda-Saad
Nov 17, 2020·Frontiers in Oncology·Patrizia LeoneVito Racanelli
Dec 12, 2020·Frontiers in Immunology·Helmi AlfarraTony Reiman
Nov 19, 2020·Journal for Immunotherapy of Cancer·Piera Filomena FioreBruno Azzarone
Jan 29, 2021·Frontiers in Pharmacology·Yaoyao ShiCara Haymaker

Methods Mentioned

BETA
flow cytometry
ISS
FACS
density gradient centrifugation
flow
genotyping

Clinical Trials Mentioned

NCT02557516
NCT02921685

Related Concepts

HLA-E*01:01 antigen
Immunologic Tumoricidal Activities
Interferon Type II
RU 49637
Natural Killer Cells
Lymphocyte Activation
Multiple Myeloma
Transplantation, Autologous
Human Class I Antigens
Hemopoietic Stem Cell Transplant

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