Abstract
Natural killer T (NKT) cells are a unique subset of lymphocytes that recognize lipid antigens in the context of the non-classical class I MHC molecule, CD1d, and serve as a link between the innate and adaptive immune system through their expeditious release of cytokines. Whereas NKT have well-established roles in mitigating a number of human diseases, herein, we focus on their role in cancer. NKT cells have been shown to directly and indirectly mediate anti-tumor immunity and manipulating their effector functions can have therapeutic significances in treatment of cancer. In this review, we highlight several therapeutic strategies that have been used to harness the effector functions of NKT cells to target different types of solid tumors. We also discuss several barriers to the successful utilization of NKT cells and summarize effective strategies being developed to harness the unique strengths of this potent population of T cells. Collectively, studies investigating the therapeutic potential of NKT cells serve not only to advance our understanding of this powerful immune cell subset, but also pave the way for future treatments focused on the modulation of NKT cell responses to enhance cancer immunotherapy.
Highlights
A hallmark of cancerous cells is their ability to evade destruction by the immune system [1]
Natural killer T (NKT) cell-mediated cytokine production leads to the induction of both the innate and adaptive immune responses; NKT cells have been implicated in the modulation of immune responses to cancer, autoimmunity, infection, allergy, and transplantation
The authors found that treatment with DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) resulted in an increase in both CD1d mRNA and protein levels in Non-small cell lung cancer (NSCLC) cell lines, sensitizing the cells to NKT cell mediated killing
Summary
A hallmark of cancerous cells is their ability to evade destruction by the immune system [1] This is essential for the tumor because the host immune system possesses the potential to eliminate malignancies, and invokes a multi-layered process that can include early recognition events by mediators of innate immunity, followed by the development of a strong and highly specific adaptive immune response. Unlike classic MHC-restricted T cells, NKT cells acquire their effector functions during development, and their activation following recognition of antigens presented in the context of CD1d molecules results in the rapid production of large amounts of effector cytokines [6]. Type II NKT cells are CD1d-restricted, but are unresponsive to α-GalCer [26,27] They have been investigated experimentally using CD1d-tetramers loaded with other lipid antigens, phospholipids, sphingolipids, and glycerolipids. We review studies focused primarily on the modulation of human type I iNKT cells in specific types of solid tumors, discuss barriers that block their therapeutic efficacy, and suggest potential strategies that can be employed to effectively target NKT cells in cancer immunotherapeutic strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
