Natural Killer T and Natural Killer Cell-Based Immunotherapy Strategies Targeting Cancer

Author:

Iyoda Tomonori1,Yamasaki Satoru1,Ueda Shogo1,Shimizu Kanako12,Fujii Shin-ichiro12ORCID

Affiliation:

1. Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan

2. RIKEN Program for Drug Discovery and Medical Technology Platforms, Yokohama 230-0045, Japan

Abstract

Both natural killer T (NKT) and natural killer (NK) cells are innate cytotoxic lymphoid cells that produce inflammatory cytokines and chemokines, and their role in the innate immune response to tumors and microorganisms has been investigated. Especially, emerging evidence has revealed their status and function in the tumor microenvironment (TME) of tumor cells. Some bacteria producing NKT cell ligands have been identified to exert antitumor effects, even in the TME. By contrast, tumor-derived lipids or metabolites may reportedly suppress NKT and NK cells in situ. Since NKT and NK cells recognize stress-inducible molecules or inhibitory molecules on cancer cells, their status or function depends on the balance between inhibitory and activating receptor signals. As a recent strategy in cancer immunotherapy, the mobilization or restoration of endogenous NKT or NK cells by novel vaccines or therapies has become a focus of research. As a new biological evidence, after activation, effector memory-type NKT cells lasted in tumor-bearing models, and NK cell-based immune checkpoint inhibition potentiated the enhancement of NK cell cytotoxicity against cancer cells in preclinical and clinical trials. Furthermore, several new modalities based on the characteristics of NKT and NK cells, including artificial adjuvant vector cells, chimeric antigen receptor-expressing NK or NKT cell therapy, or their combination with immune checkpoint blockade have been developed. This review examines challenges and future directions for improving these therapies.

Funder

RIKEN

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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