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

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.

Mesenchymal Stromal Cells Increase the Natural Killer Resistance of Circulating Tumor Cells via Intercellular Signaling of cGAS‐STING‐IFNβ‐HLA

“…The immune system, including NK and T cells, plays a key role in controlling metastatic disease and destroying metastatic colonies. [ 76 ] It has been reported that NK and T cells preferentially exert distinct roles in immunosurveillance at different stages of tumor progression. [ 77 ] To evade immunosurveillance, cancer cells dynamically change HLA‐I levels to alter their susceptibility to T cells or NK cells.…”

Harnessing Metformin’s Immunomodulatory Effects on Immune Cells to Combat Breast Cancer

“…NKT cells represent a unique subset of CD1d-restricted T cells that serve as a crucial bridge between the innate and adaptive branches of the immune system [ 7 ]. These cells exhibit a remarkable capacity to quickly respond to a diverse array of glycolipids and stress-related proteins through mechanisms characteristic of both T cells and NK cells [ 24 ]. Given their ability to significantly influence immune responses through the secretion of various cytokines, NKT cells play a pivotal role in the immunological surveillance against tumors [ 25 ].…”

Outsmarting trogocytosis to boost CAR NK/T cell therapy

“…The cells can distinguish between normal cells and cancerous cells by detecting the loss of expression of MHC class I molecules or expression of stress molecules during "missing-self " or "induced-self " recognition. Once an NK cell recognizes a target cell, it produces various proinflammatory and immunosuppressive cytokines and growth factors [26]. Trogocytosis has been shown to play an important role in regulating the sensitivity of NK cells to target cells.…”