NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations

Natural killer (NK) cells, the primary effector cells of the innate immune system, utilize multiple strategies to recognize tumor cells by (1) detecting the presence of activating receptor ligands, which are often upregulated in cancer; (2) targeting cells that have a loss of major histocompatibility complex (MHC); and (3) binding to antibodies that bind to tumor-specific antigens on the tumor cell surface. All these strategies have been successfully harnessed in adoptive NK cell immunotherapies targeting cancer. In this review, we review the applications of NK cell therapies across different tumor types. Similar to other forms of immunotherapy, tumor-induced immune escape and immune suppression can limit NK cell therapies' efficacy. Therefore, we also discuss how these limitations can be overcome by conferring NK cells with the ability to redirect their tumor-targeting capabilities and survive the immune-suppressive tumor microenvironment. Finally, we also discuss how future iterations can benefit from combination therapies with other immunotherapeutic agents. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Automated summary

NK cells, as primary effector cells of the innate immune system, use various strategies to recognize and target tumor cells, which have been successfully applied in adoptive NK cell immunotherapies. However, tumor-induced immune escape and suppression may limit the efficacy of these therapies, which can be overcome by conferring NK cells with new functions and surviving the immune-suppressive tumor microenvironment. Additionally, future iterations of NK cell therapies may benefit from combination therapies with other immunotherapeutic agents.