Current Developments in the Preclinical and Clinical use of Natural Killer T cells

Kratzmeier, Christina; Singh, Sasha A; Asiedu, Emmanuel B; Webb, Tonya J.

doi:10.1007/s40259-022-00572-4

Cited by 5 publications

(9 citation statements)

References 115 publications

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“…In contrast, the plasma cells play a fundamental role in tissue repair by producing antibodies ( Han et al, 2018 ; Polanco et al, 2021 ). NK cells exert a crucial function in host defense by rapidly producing cytokines and upregulating the expression of cell death-inducing molecules to eliminate infected cells ( Kratzmeier et al, 2023 ). CD57 + NK cells were presented in chronic AP lesions, and upregulated NK cells were observed in periapical granulomas compared with radicular cysts ( Silva et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Fan

Lyu

et al. 2023

eLife

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Oral inflammatory diseases such as apical periodontitis are common bacterial infectious diseases that may affect the periapical alveolar bone tissues. A protective process occurs simultaneously with the inflammatory tissue destruction, in which mesenchymal stem cells (MSCs) play a primary role. However, a systematic and precise description of the cellular and molecular composition of the microenvironment of bone affected by inflammation is lacking. In this study, we created a single cell atlas of cell populations that compose alveolar bone in healthy and inflammatory disease states. We investigated changes in expression frequency and patterns related to apical periodontitis, as well as the interactions between MSCs and immunocytes. Our results highlight an enhanced self-supporting network and osteogenic potential within MSCs during apical periodontitis-associated inflammation. MSCs not only differentiated towards osteoblast lineage cells, but also expressed higher levels of osteogenic related markers, including Sparc and Col1a1. This was confirmed by lineage tracing in transgenic mouse models and human samples from oral inflammatory-related alveolar bone lesions. In summary, the current study provides an in-depth description of the microenvironment of MSCs and immunocytes in both healthy and disease states. We also identified key apical periodontitis-associated MSC subclusters and their biomarkers, which could further our understanding of the protective process and the underlying mechanisms of oral inflammatory-related bone disease. Taken together, these results enhance our understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. We provide these data as a tool for investigators not only to better appreciate the repertoire of progenitors that are stress responsive but importantly to help design new therapeutic targets to restore bone lesions caused by apical periodontitis and other inflammatory-related bone diseases.

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Section: Discussionmentioning

confidence: 99%

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Fan

Lyu

et al. 2023

eLife

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“…iNKT expresses a constant TCR composed of Vα24Jα18 chains (TCRα) and Vβ11 chains (TCRβ) [ 36 ]. CD1d, an MHC class I protein, is capable of presenting a variety of lipid antigens to T cells [ 37 ].…”

Section: Classifications Of Ctlsmentioning

confidence: 99%

“…CD1d, an MHC class I protein, is capable of presenting a variety of lipid antigens to T cells [ 37 ]. iNKT cells differentiate predominantly in the thymus into NKT1, NKT2, NKT17, and NKT10 cells [ 36 , 38 ]. Studies have found that NKT1 cells tend to exhibit a higher level of cellular expression than other subpopulations of iNKT cells [ 38 ].…”

Section: Classifications Of Ctlsmentioning

confidence: 99%

“…Similar to classical T-cell subsets, NKT cells develop in the thymus, but NKTs diverge as they enter the DP phase [ 71 ]. iNKT differentiation depends on the binding between the TCR and CD1d to initiate the NKT cell developmental program, which is further differentiated under early growth response 2 (Egr-2) and promyelocytic leukemia zinc finger (PLZF) selection [ 36 ]. iNKT cells can be divided into subpopulations similar to CD4+ Th cells.…”

Section: Origin and Differentiation Trajectory Of Ctlsmentioning

confidence: 99%

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CTLs heterogeneity and plasticity: implications for cancer immunotherapy

Peng,

Lin,

Jiang

et al. 2024

Mol Cancer

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Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.

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“…They may also trigger the effector Th 1 cells and CD8 + T cells, as well as favour the conversion of Th 2 to Th 1 in the secondary lymphoid tissues and tumour microenvironment, thus inhibiting cancer growth. These findings suggest that activation of NKT cells may provide an effective anti-cancer outcome [ 280 , 281 , 282 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

Starska

2023

Cancers

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Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive and heterogeneous groups of human neoplasms. HNSCC is characterized by high morbidity, accounting for 3% of all cancers, and high mortality with ~1.5% of all cancer deaths. It was the most common cancer worldwide in 2020, according to the latest GLOBOCAN data, representing the seventh most prevalent human malignancy. Despite great advances in surgical techniques and the application of modern combinations and cytotoxic therapies, HNSCC remains a leading cause of death worldwide with a low overall survival rate not exceeding 40–60% of the patient population. The most common causes of death in patients are its frequent nodal metastases and local neoplastic recurrences, as well as the relatively low response to treatment and severe drug resistance. Much evidence suggests that the tumour microenvironment (TME), tumour infiltrating lymphocytes (TILs) and circulating various subpopulations of immunocompetent cells, such regulatory T cells (CD4+CD25+Foxp3+Tregs), cytotoxic CD3+CD8+ T cells (CTLs) and CD3+CD4+ T helper type 1/2/9/17 (Th1/Th2/Th9/Th17) lymphocytes, T follicular helper cells (Tfh) and CD56dim/CD16bright activated natural killer cells (NK), carcinoma-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (N1/N2 TANs), as well as tumour-associated macrophages (M1/M2 phenotype TAMs) can affect initiation, progression and spread of HNSCC and determine the response to immunotherapy. Rapid advances in the field of immuno-oncology and the constantly growing knowledge of the immunosuppressive mechanisms and effects of tumour cancer have allowed for the use of effective and personalized immunotherapy as a first-line therapeutic procedure or an essential component of a combination therapy for primary, relapsed and metastatic HNSCC. This review presents the latest reports and molecular studies regarding the anti-tumour role of selected subpopulations of immunocompetent cells in the pathogenesis of HNSCC, including HPV+ve (HPV+) and HPV−ve (HPV−) tumours. The article focuses on the crucial regulatory mechanisms of pro- and anti-tumour activity, key genetic or epigenetic changes that favour tumour immune escape, and the strategies that the tumour employs to avoid recognition by immunocompetent cells, as well as resistance mechanisms to T and NK cell-based immunotherapy in HNSCC. The present review also provides an overview of the pre- and clinical early trials (I/II phase) and phase-III clinical trials published in this arena, which highlight the unprecedented effectiveness and limitations of immunotherapy in HNSCC, and the emerging issues facing the field of HNSCC immuno-oncology.

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Current Developments in the Preclinical and Clinical use of Natural Killer T cells

Cited by 5 publications

References 115 publications

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

CTLs heterogeneity and plasticity: implications for cancer immunotherapy

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

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