Histone deacetylase inhibitors enhance CD1d-dependent NKT cell responses to lymphoma.

Histone deacetylases (HDACs) are a family of enzymes that influence expression of genes implicated in tumor initiation, progression, and anti-tumor responses. In addition to their canonical role in deacetylation of histones, HDACs regulate many non-canonical targets, such as Signal Transducer and Activator of Transcription 3 (STAT3). We hypothesize that tumors use epigenetic mechanisms to dysregulate CD1d-mediated antigen presentation, thereby impairing the ability of natural killer T (NKT) cells to recognize and destroy malignant cells.

Immunotherapeutic strategies targeting natural killer T cell responses in cancer.

Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans.

Sphingosine 1-phosphate signaling impacts lymphocyte migration, inflammation and infection.

Sphingosine 1-phosphate (S1P) is a sphingosine containing lipid intermediate obtained from ceramide. S1P is known to be an important signaling molecule and plays multiple roles in the context of immunity. This lysophospholipid binds and activates G-protein-coupled receptors (GPCRs) known as S1P receptors 1-5 (S1P1-5).

VEGF Potentiates GD3-Mediated Immunosuppression by Human Ovarian Cancer Cells.

Purpose: Natural killer T (NKT) cells are important mediators of antitumor immune responses. We have previously shown that ovarian cancers shed the ganglioside GD3, which inhibits NKT-cell activation. Ovarian cancers also secrete high levels of VEGF.

NKT Cell Responses to B Cell Lymphoma.

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic.