Invariant NKT Cell-Based Vaccine Strategies

Jukes, John‐Paul; Silk, Jonathan D.; Salio, Mariolina; Cerundolo, Vincenzo

doi:10.1007/978-1-4614-0613-6_3

Cited by 2 publications

(3 citation statements)

References 96 publications

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“…iNKT cells can also directly provide B-cell help through CD1d expression on B cells [69, 70]. This ability to prime the adaptive immune response indicates that iNKT-cell agonists could be used in the clinic to harness iNKT cells, where they have previously been shown to have adjuvant effects in combination with a number of vaccines [71]. iNKT cells can be activated via soluble factors (indirect NKT-cell activation) released by TLR-activated DCs, such as type I IFN, IL12, and IL18 [44, 45, 51, 72-75], or by co-stimulatory molecules like OX40/OX40L [76].…”

Section: Inkt-cell Activation and Down-stream Signallingmentioning

confidence: 99%

Section: Inkt-cell Activation and Down-stream Signallingmentioning

confidence: 99%

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The Regulatory Role of Invariant NKT Cells in Tumor Immunity

McEwen-Smith

Salio

Cerundolo

2015

Cancer Immunology Research

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126

102

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Invariant natural killer T (iNKT) cells are a unique population of T lymphocytes, which lie at the interface between the innate and adaptive immune systems, and are important mediators of immune responses and tumor surveillance. iNKT cells recognize lipid antigens in a CD1d-dependent manner; their subsequent activation results in a rapid and specific downstream response, which enhances both innate and adaptive immunity. The capacity of iNKT cells to modify the immune microenvironment influences the ability of the host to control tumor growth, making them an important population to be harnessed in the clinic for the development of anticancer therapeutics. Indeed, the identification of strong iNKT-cell agonists, such as a-galactosylceramide (a-GalCer) and its analogues, has led to the development of synthetic lipids that have shown potential in vaccination and treatment against cancers. In this Masters of Immunology article, we discuss these latest findings and summarize the major discoveries in iNKT-cell biology, which have enabled the design of potent strategies for immune-mediated tumor destruction.Cancer Immunol Res; 3(5); 425-35. Ó2015 AACR. Disclosure of Potential Conflicts of InterestNo potential conflicts of interest were disclosed. Editor's DisclosuresThe following editor(s) reported relevant financial relationships. G. Dranoff-None. CME Staff Planners' DisclosuresThe members of the planning committee have no real or apparent conflicts of interest to disclose. Learning ObjectivesResearch on the fundamental aspects of ab T-cell receptor (TCR) structure and function has informed infectious disease and oncology disciplines about the nature of cognate antigen recognition by the T-cell adaptive immune system. This information, in turn, will lead to effective development of CD8 T cell-based vaccines for preventive and immunotherapeutic purposes. Upon completion of this activity, the participant should gain a basic knowledge of the molecular structure of the ab TCR and the mechanobiology that allows a TCR to recognize a distinct foreign peptide among a myriad of antigens bound to the major histocompatibility complex with the required sensitivity and specificity for host protection.

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Section: Inkt-cell Activation and Down-stream Signallingmentioning

confidence: 99%

Section: Inkt-cell Activation and Down-stream Signallingmentioning

confidence: 99%

The Regulatory Role of Invariant NKT Cells in Tumor Immunity

McEwen-Smith

Salio

Cerundolo

2015

Cancer Immunology Research

Self Cite

126

102

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“…IFN-γ and IL-4) and recruitment of dendritic cells (DC), NK cells, B cells, helper T cells, and cytotoxic T cells. In mice, this capability of αGC-stimulated iNKT cells to boost cellular immune responses was strong enough to generate specific responses against tumor cells, such as the B16F10 melanoma cell line, leading to long-term tumor rejection ( 5 – 7 ). Besides this adjuvant effect, iNKT cells can also directly control tumor growth by cytotoxicity ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC

Caumartin

Amodio

et al. 2021

Front. Immunol.

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Invariant Natural Killer T (iNKT) cells are a small and distinct population of T cells crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance specific anti-tumor activity. Several human clinical trials on iNKT cell-based anti-cancer are ongoing, however results are not as striking as in murine models. Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known immune checkpoint molecule involved in fetal-maternal tolerance and in tumor immune escape. HLA-G exerts its immunomodulatory functions through the interaction with immune inhibitory receptors such as ILT2, differentially expressed on immune cell subsets. We hypothesized that HLA-G might inhibit iNKT function directly or by inducing tolerogenic APC leading to iNKT cell anergy, which could impact the results of current clinical trials. Using an ILT2-transduced murine iNKT cell line and human iNKT cells, we demonstrate that iNKT cells are sensitive to HLA-G, which inhibits their cytokine secretion. Furthermore, human HLA-G+ dendritic cells, called DC-10, failed at inducing iNKT cell activation compared to their autologous HLA-G‒ DCs counterparts. Our data show for the first time that the HLA-G/ILT2 ICP is involved in iNKT cell function modulation.

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Invariant NKT Cell-Based Vaccine Strategies

Cited by 2 publications

References 96 publications

The Regulatory Role of Invariant NKT Cells in Tumor Immunity

The Regulatory Role of Invariant NKT Cells in Tumor Immunity

Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC

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