Induced pluripotency as a potential path towards iNKT cell-mediated cancer immunotherapy

  title={Induced pluripotency as a potential path towards iNKT cell-mediated cancer immunotherapy},
  author={Hiroshi Watarai and Daisuke Yamada and Shin-ichiro Fujii and Masaru Taniguchi and Haruhiko Koseki},
  journal={International Journal of Hematology},
Invariant natural killer T (iNKT) cells are characterized by the expression of an invariant Vα14–Jα18 paired with Vβ8/7/2 in mice, and Vα24–Jα18 with Vβ11 in humans, that recognizes glycolipids, such as α-galactosylceramide (α-GalCer), presented on the MHC class I-like molecule, CD1d. iNKT cells act as innate T lymphocytes and serve as a bridge between the innate and acquired immune systems. iNKT cells augment anti-tumor responses by producing IFN-γ, which acts on NK cells to eliminate MHC-non… 

The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

There should be three important focuses of future research in cancer patients in relation with NKT cells: expansion of the N KT cell population, prevention and breaking of NKT cell anergy, and skewing of N KT cells toward TH1-like subsets with antitumor activity.

Elucidation and Control of the Mechanisms Underlying Chronic Inflammation Mediated by Invariant Natural Killer T Cells

Understanding of CD1d-restricted iNKT cells contributes to their true potentials in immunotherapeutic applications for various diseases and their roles in pathological inflammation are discussed.

[Pluripotent stem cells as a source for T cell research and clinical application].

  • Tatsuki UedaS. Kaneko
  • Biology
    Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
  • 2015
Recently, promising clinical outcomes of cancer immunotherapy including administration of an anti PD-1 antibody targeting for T cell reactivation has gained particular attention worldwide. Adoptive

Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells

This pilot study shows that adoptive transfer and in vivo expansion of haploidentical γδ T lymphocytes is feasible and suggests a potential role of these cells in the treatment of haematological diseases.

Vaccination with vascular progenitor cells derived from induced pluripotent stem cells elicits antitumor immunity targeting vascular and tumor cells

Results suggest that iVP cells from iPS cells could be used as a cancer vaccine targeting tumor vascular cells and tumor cells.

Immunogenicity and Tumorigenicity of Pluripotent Stem Cells and their Derivatives: Genetic and Epigenetic Perspectives

As induced PSC-based therapy represents a hallmark for the potential solution to prevent and arrest immune rejection, this review also summarizes several up-to-date key findings in the field.

Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

The recent advances in hiPSCs' basic research and some potential clinical applications focusing on cancer are shown and the importance of the use of statistical methods to evaluate the possible validation for the hiPSC for future therapeutic use toward personalized cell therapies is presented.

Generation of iPS cells from normal and malignant hematopoietic cells

iPSCs from hematological malignancies have been established only from myeloproliferative neoplasms including chronic myelogenous leukemia (CML) and JAK2-V617F mutation-positive polycythemia vera (PV).

Clinical Applications of Induced Pluripotent Stem Cells in Cancer

The recent advances in hiPSCs’ basic research and some potential clinical applications in cancer are shown and the importance in using statistical methods to evaluate the possible validation of hiPSC for therapeutic use is presented.

Activation of EL-4 T-cells by irradiation with atmospheric oxygen plasma

Gene expression analysis of T-cell supports results of the proliferation and the immune function enhancements and the plasma irradiation promotes cell proliferation.



Clinical applications of natural killer T cell–based immunotherapy for cancer

The quantitative alteration and functional deterioration of circulating Vα24 NKT cells in various cancer‐bearing patients and the recent progress in the clinical studies of NKT cell‐based tumor immunotherapy are summarized.

Innate Vα14+ natural killer T cells mature dendritic cells, leading to strong adaptive immunity

Findings help explain tumor protection via α‐GalCer and urge development of the DC‐NKT axis to provide innate and adaptive immunity to human cancers.

Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells.

The feasibility of expanding functionally competent NKT cells via an iPSC phase is demonstrated, an approach that may be adapted for NKT cell-targeted therapy in humans.

Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide.

It is reported that dendritic cells (DCs) pulsed with alpha-GalCer effectively induce potent antitumor cytotoxic activity by specific activation of Valpha14 NKT cells, resulting in the inhibition of tumor metastasis in vivo.

Therapeutic activation of Vα24^+Vβ11^+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity

The first clinical evidence that Valpha24(+)Vbeta11(+) NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation is presented.

Positive selection of mouse NK1+ T cells by CD1-expressing cortical thymocytes

  • A. Bendelac
  • Biology
    The Journal of experimental medicine
  • 1995
Mouse NK1+ T cells constitute a subset of alpha/beta TCR+ T cells that specialize in the rapid production of cytokines, in particular IL-4, and may promote the differentiation of Th2-type CD4 T

The Natural Killer T (NKT) Cell Ligand α-Galactosylceramide Demonstrates Its Immunopotentiating Effect by Inducing Interleukin (IL)-12 Production by Dendritic Cells and IL-12 Receptor Expression on NKT Cells

Findings indicate an important role for DC-produced IL-12 in the activation of NKT cells by α-GalCer and suggest that N KT cells may be able to condition DCs for subsequent immune responses and suggest a novel approach for immunotherapy of cancer.

Tumor-host immune interactions and dendritic cell dysfunction.

A Novel Function of Vα14+CD4+NKT Cells: Stimulation of IL-12 Production by Antigen-Presenting Cells in the Innate Immune System

It is demonstrated that Ag-activated CD4+ NKT cells express CD40 ligand (CD40L) (CD154), which engages CD40 on APC and stimulates them to produce IL-12, a novel function of CD4-NKT cells that could be involved in the regulation of Th1 vs Th2 development.

α-Galactosylceramide-activated Vα14 natural killer T cells mediate protection against murine malaria.

The results provide the clear evidence that NKT cells can mediate protection against an intracellular microbial infection.