Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential
1
Medical Science Training Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
2
Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
3
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
*
Authors to whom correspondence should be addressed.
Cancers 2022, 14(23), 5787; https://doi.org/10.3390/cancers14235787
Submission received: 6 October 2022
/
Revised: 7 November 2022
/
Accepted: 21 November 2022
/
Published: 24 November 2022
(This article belongs to the Special Issue Natural Killer Cells in Cancer Biology and Therapy)
Simple Summary
Natural killer (NK) cells are immune cells with potent anti-tumor and anti-infection activity. The potential benefit of NK cell therapy against chronic lymphocytic leukemia (CLL) has long been recognized, but efforts to develop effective NK cell therapies have been hampered by multiple factors including the immunosuppressive effects of CLL against NK cells. In this review, we first outline the specific NK cell impairment seen in CLL and the known mechanisms causing these defects. We then discuss the NK-altering effects of current CLL therapeutics as well as the past and present progress towards developing NK cell therapy for CLL.
Abstract
Immunotherapy approaches have advanced rapidly in recent years. While the greatest therapeutic advances so far have been achieved with T cell therapies such as immune checkpoint blockade and CAR-T, recent advances in NK cell therapy have highlighted the therapeutic potential of these cells. Chronic lymphocytic leukemia (CLL), the most prevalent form of leukemia in Western countries, is a very immunosuppressive disease but still shows significant potential as a target of immunotherapy, including NK-based therapies. In addition to their antileukemia potential, NK cells are important immune effectors in the response to infections, which represent a major clinical concern for CLL patients. Here, we review the interactions between NK cells and CLL, describing functional changes and mechanisms of CLL-induced NK suppression, interactions with current therapeutic options, and the potential for therapeutic benefit using NK cell therapies.
