Novel lipid antigens for NKT cells in cancer

Abstract

Cancer immunotherapy aims to unleash the power of the immune system against tumors without the side effects of traditional chemotherapy. Immunotherapeutic methods vary widely, but all follow the same basic principle: overcome the barriers utilized by cancers to avoid immune destruction. These approaches often revolve around classical T cells, such as with CAR T cells and neoantigen vaccines; however, the utility of the innate-like iNKT cell in cancer immunotherapy has gained significant recognition. iNKT cells parallel classic T cell recognition of peptide antigens presented on MHC through their recognition of lipid antigens presented on the MHC I-like molecule CD1d. Altered metabolism and a lipogenic phenotype are essential properties of tumor cells, representing a unique feature that may be exploited by iNKT cells. In this review, we will cover properties of iNKT cells, CD1d, and lipid antigen presentation. Next, we will discuss the cancer lipidome and how it may be exploited by iNKT cells through a window of opportunity. Finally, we will review, in detail, novel lipid antigens for iNKT cells in cancer.

Immune-profiling of T helper 1 (Th1), Th2 and Th17 signatures in murine splenocytes by targeting intracellular cytokines

“…Mainly NKT cells and γδT cells play a key role in the innate immune system despite there being reports of their involvement in triggering adaptive type memory responses through cytokine production (13)(14)(15). γδ T cells with an innate receptor (NK1.1 or NKp46), termed as γδNKT cells are believed to play a role in both innate and adaptive immunity, possibly in recognizing lipid antigens (16,17).…”

Human CD4+iNKT cell adoptive immunotherapy induces anti‐tumour responses against CD1d‐negative EBV‐driven B lymphoma

“…In contrast, presentation of self lipids is able to induce iNKT cell cytokine secretion, but is typically less effective for promoting cytotoxicity [34,40,41]. Neoplastic transformation may be associated with lipidomic changes that generate more highly potent antigens, however, this may be counterbalanced by downregulation of CD1d molecules or other compensatory changes that reduce the antigenicity of tumour cells for iNKT cells [42]. Hence, since evasive events are likely to accrue in tumours over time, iNKT targeting of tumour cells for direct cytolysis through TCRmediated recognition of CD1d may be limited in clinical settings, but alternative anti-tumour pathways may be maintained.…”