Invariant Natural Killer T Cells in Immune Regulation of Blood Cancers: Harnessing Their Potential in Immunotherapies

Lam, Pui Yeng; Nissen, Michael; Mattarollo, Stephen R.

doi:10.3389/fimmu.2017.01355

Cited by 29 publications

(20 citation statements)

References 159 publications

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“…Natural killer cells and natural killer T (NKT) cells are subsets of lymphocytes and can respond to the presence of tumor cells and participate in antitumor immune responses [81]. Invariant natural killer T (iNKT) cells are a unique innate T lymphocyte population which plays an important role in the immune surveillance of blood cancers [82]. NK cell dysfunctions have been observed in various hematologic malignancies, including chronic lymphocytic leukemia (CLL) through soluble ligand BAG6/-BAT3.…”

Section: Tex Suppress Nk Cellmentioning

confidence: 99%

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

Olejarz

Dominiak

Żołnierzak

et al. 2020

Journal of Immunology Research

100

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Tumor-derived exosomes (TEX) are involved in cancer development, metastasis, and disease progression. They can modulate angiogenesis to elevate the malignant degree of tumor cells. TEX carry immunosuppressive factors affecting the antitumor activities of immune cells. Tumor cells as well as immune cells secrete immunologically active exosomes which affect intercellular communication, antigen presentation, activation of immune cells, and immune surveillance. Cell proliferation and immune response suppression create a favorable microenvironment for tumor. TEX can inhibit immune cell proliferation, induce apoptosis of activated CD8+ Teffs, suppress NK cell activity, interfere with monocyte differentiation, and promote Treg as well as MDSC expansion. Exosomes of microenvironment cells may also contribute to the development of drug resistance in cancer therapy. An important role of TEX in modulating the sensitivity of tumor cells to immunotherapy is a promising area of research to make the cancer therapy more successful.

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Section: Tex Suppress Nk Cellmentioning

confidence: 99%

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

Olejarz

Dominiak

Żołnierzak

et al. 2020

Journal of Immunology Research

100

View full text Add to dashboard Cite

show abstract

“…Tregs are heterogeneous in the periphery 8,9 . Despite the discovery of various Treg subtypes such as type 1 regulatory T (Tr1) 10,11 , CD8 + 12,13 , CD4 + CD25 − LAG3 + 14,15 , γδ TCR + 16,17 and invariant natural killer T (iNKT) 18,19 regulatory cells, CD4 + FoxP3 + Tregs remain as the principal target of investigation in humans and mice 20,21 . CD4 + CD25 + FoxP3 + T cells in mice are suppressive 20,22 , whereas accumulating evidence suggests that CD4 + FoxP3 + T cells in humans are heterogeneous in phenotype and function 23–25 .…”

Section: Introductionmentioning

confidence: 99%

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Chang

Stell

et al. 2019

Sci Rep

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Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function.

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“…UCB transplants have demonstrated remarkable effectiveness in treating many types of blood cancers. Adoptive transfer of NKT cells has been tested in animal models [74, 75], and several clinical trials are underway to test the safety and efficiency of NKT-cell transfer to harness solid tumors in humans [76–79]. Enhanced understanding of NKT-cell heterogeneity in UCB would benefit our selection of appropriate sources, and activation of the cytotoxicity of NKT cells to target cancer and other diseases.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic landscape of nucleated cells in umbilical cord blood

Zhao

et al. 2019

GigaScience

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Background For both pediatric and adult patients, umbilical cord blood (UCB) transplant is a therapeutic option for a variety of hematologic diseases, such as blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in UCB has not yet been assessed in an unbiased and systemic fashion. In the present study, nucleated cells from UCB were subjected to single-cell RNA sequencing to simultaneously profile the gene expression signatures of thousands of cells, generating a rich resource for further functional studies. Here, we report the transcriptomes of 17,637 UCB cells, covering 12 major cell types, many of which can be further divided into distinct subpopulations. Results Pseudotemporal ordering of nucleated red blood cells identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect nucleated red blood cell maturation. Progenitor cells in UCB also comprise 2 subpopulations with activation of divergent transcription programs, leading to specific cell fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in natural killer and natural killer T-cell types in UCB. Conclusions Taken together, our data form a comprehensive single-cell transcriptomic landscape that reveals previously unrecognized cell types, pathways, and mechanisms of gene expression regulation. These data may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.

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Invariant Natural Killer T Cells in Immune Regulation of Blood Cancers: Harnessing Their Potential in Immunotherapies

Cited by 29 publications

References 159 publications

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Single-cell transcriptomic landscape of nucleated cells in umbilical cord blood

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