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


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


Sep 1, 1990·European Journal of Haematology·A OsterborgH Mellstedt
Jan 1, 1997·International Journal of Clinical & Laboratory Research·M A FrassanitoF Dammacco
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·N LeeD E Geraghty
Mar 9, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Franco AversaMassimo F Martelli
Sep 13, 2006·Journal of Leukocyte Biology·Katy WendtRoland Jacobs
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chiara RomagnaniGuido Ferlazzo
Sep 26, 2009·Clinical Lymphoma & Myeloma·Sergio Giralt
Nov 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Esther M de KruijfPeter J K Kuppen
Mar 23, 2012·Nature Reviews. Immunology·Eric VivierLaurent Brossay
Jan 15, 2013·Frontiers in Immunology·Stephanie Krieg, Evelyn Ullrich
May 31, 2013·Journal of Immunotherapy·Michael A SheardRobert C Seeger
Dec 20, 2013·Oncoimmunology·Evelyn UllrichAlexander Steinle
Apr 30, 2015·Cancer Immunology, Immunotherapy : CII·Subhashis SarkarLotte Wieten
May 23, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Don M BensonMichael A Caligiuri
Dec 5, 2015·Frontiers in Immunology·Katayoun Rezvani, Rayne H Rouce
Dec 5, 2015·Frontiers in Immunology·Benedikt JacobsEvelyn Ullrich
Jun 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mattias CarlstenRichard W Childs
Feb 3, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ola Landgren, S Vincent Rajkumar
May 11, 2017·Frontiers in Immunology·Federico SimonettaRobert S Negrin
May 12, 2017·Frontiers in Immunology·Markus GranzinEvelyn Ullrich
Dec 28, 2017·Critical Reviews in Oncology/hematology·Gordon CookPhilippe Moreau
Feb 20, 2018·Frontiers in Immunology·Nicole A P LiebermanCourtney A Crane


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

flow cytometry
density gradient centrifugation

Clinical Trials Mentioned


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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