Abstract
Invariant natural killer T (iNKT) cells are a unique innate T lymphocyte population that possess cytolytic properties and profound immunoregulatory activities. iNKT cells play an important role in the immune surveillance of blood cancers. They predominantly recognize glycolipid antigens presented on CD1d, but their activation and cytolytic activities are not confined to CD1d expressing cells. iNKT cell stimulation and subsequent production of immunomodulatory cytokines serve to enhance the overall antitumor immune response. Crucially, the activation of iNKT cells in cancer often precedes the activation and priming of other immune effector cells, such as NK cells and T cells, thereby influencing the generation and outcome of the antitumor immune response. Blood cancers can evade or dampen iNKT cell responses by downregulating expression of recognition receptors or by actively suppressing or diverting iNKT cell functions. This review will discuss literature on iNKT cell activity and associated dysregulation in blood cancers as well as highlight some of the strategies designed to harness and enhance iNKT cell functions against blood cancers.
Highlights
Blood cancers are a heterogeneous group of malignancies broadly encompassing leukemia, myeloma, and lymphoma
Invariant natural killer T cells recognize glycolipid antigens presented on the MHC Class I-like molecule CD1d, which are expressed on many cell types, but most highly expressed on antigen-presenting cells (APCs) [40, 41]
In a more recent study, Lu et al [99] demonstrated that antibody blockade of soluble MHC class I chain-related (MIC) in a model of adenocarcinoma could potentiate IFNγ production upon stimulation [100] As elevated levels of soluble NKG2D ligands in the plasma of patients with MM, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), Hodgkin’s lymphoma (HL), and non-HL have been observed [101,102,103,104,105], it is predicted that NKG2D-expressing Invariant natural killer T (iNKT) cells will be dysregulated in these tumor microenvironments
Summary
INKT cells play an important role in the immune surveillance of blood cancers. They predominantly recognize glycolipid antigens presented on CD1d, but their activation and cytolytic activities are not confined to CD1d expressing cells. INKT cell stimulation and subsequent production of immunomodulatory cytokines serve to enhance the overall antitumor immune response. Blood cancers can evade or dampen iNKT cell responses by downregulating expression of recognition receptors or by actively suppressing or diverting iNKT cell functions. This review will discuss literature on iNKT cell activity and associated dysregulation in blood cancers as well as highlight some of the strategies designed to harness and enhance iNKT cell functions against blood cancers
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
