CD8+CD161+ T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential

Konduri, Vanaja; Oyewole-Said, Damilola; Vazquez‐Perez, Jonathan; Weldon, Scott A.; Halpert, Matthew M.; Levitt, Jonathan M.; Decker, William K.

doi:10.3389/fimmu.2020.613204

Cited by 65 publications

(82 citation statements)

References 82 publications

(142 reference statements)

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“…CD161 is expressed on natural killer cells, subsets of CD4 + and CD8 + T cells (4). A recent study using single-cell RNA sequencing of tumour-infiltrating T cells discovered that CD161 acts as a potential inhibitory receptor in liver cancer and glioma.…”

Section: Introductionmentioning

confidence: 99%

A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint

Zhou

Liu

et al. 2021

Front. Immunol.

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BackgroundCD161, encoded by killer cell lectin-like receptor B1 gene, is a newly reported candidate inhibitor of tumour-infiltrating T cells. Antibody-mediated CD161 blockade enhances T cell-mediated killing of cancer cells in vitro and in vivo in several tumour types. We evaluated the role of CD161 using The Cancer Genome Atlas (TCGA) Pan-Cancer Data.MethodsCD161 expression was analysed using RNAseq data from TCGA and the Genotype-Tissue Expression (GTEx) database. HPA, GeneCards, and String database were used to explore the protein information of CD161. The prognostic value of CD161 was analysed using clinical survival data from the TCGA. Enrichment analysis of CD161 was conducted using the R package “clusterProfiler”. We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CD161 expression. We further assessed the association between CD161 and immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.FindingsCD161 was differentially expressed and predicted better survival status in most tumour types in TCGA. In addition, CD161 expression was significantly associated with immunoregulatory interactions between lymphoid and non-lymphoid cells. CD161 expression was closely correlated with T cell infiltration, immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors.InterpretationOur results suggest that CD161 is a potential cancer biomarker. CD161 might synergize with other immune checkpoints to regulate the immune microenvironment, which could be applied in the development of new-targeted drugs for immunotherapy.FundingThis work was supported by the National Nature Science Foundation of China (grant numbers 81773008, 81672756, 81872399, 81972897), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015), the Natural Science Foundation of Guangdong Province (grant number 2017A030311023), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program: 2017BT01S131 and the Guangzhou Technology Project (grant number 201804010044), National Key R&D Program of China (Grant Nos. 2020YFC2006400), Key-Area Research and Development Program of Guangdong Province (2019B020227004).

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Section: Introductionmentioning

confidence: 99%

A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint

Zhou

Liu

et al. 2021

Front. Immunol.

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“…To further examine innate-like T cells and their capacity to enter specific tissues, we studied tissue-homing receptors. First, we focused on the tissue-homing receptor CD161, which is expressed on NK cells but also on several T cell subsets ( 23 ). We found a lower percentage of innate-like T cells expressing CD161 post-aHSCT than pre-aHSCT ( Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

“…NKR-P1A, also referred to as CD161, is a homodimer belonging to the C-type lectin family and is expressed by most NK cells ( 68 ). CD161 expression on T cells can be inhibitory, stimulatory, or act as a survival signal ( 23 ). Furthermore, it has been associated with tissue homing, cytotoxicity and a memory phenotype ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…CD161 expression on T cells can be inhibitory, stimulatory, or act as a survival signal ( 23 ). Furthermore, it has been associated with tissue homing, cytotoxicity and a memory phenotype ( 23 ). CD161 expression distinguishes conventional and innate-like T cells, with low expression on conventional T cells and high expression on innate-like T cells.…”

Section: Discussionmentioning

confidence: 99%

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NK Cells and Innate-Like T Cells After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

et al. 2021

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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which autoreactive T and B cells play important roles. Other lymphocytes such as NK cells and innate-like T cells appear to be involved as well. To name a few examples, CD56bright NK cells were described as an immunoregulatory NK cell subset in MS while innate-like T cells in MS were described in brain lesions and with proinflammatory signatures. Autologous hematopoietic stem cell transplantation (aHSCT) is a procedure used to treat MS. This procedure includes hematopoietic stem/progenitor cell (HSPC) mobilization, then high-dose chemotherapy combined with anti-thymocyte globulin (ATG) and subsequent infusion of the patients own HSPCs to reconstitute a functional immune system. aHSCT inhibits MS disease activity very effectively and for long time, presumably due to elimination of autoreactive T cells. Here, we performed multidimensional flow cytometry experiments in peripheral blood lymphocytes of 27 MS patients before and after aHSCT to address its potential influence on NK and innate-like T cells. After aHSCT, the relative frequency and absolute numbers of CD56bright NK cells rise above pre-aHSCT levels while all studied innate-like T cell populations decrease. Hence, our data support an enhanced immune regulation by CD56bright NK cells and the efficient reduction of proinflammatory innate-like T cells by aHSCT in MS. These observations contribute to our current understanding of the immunological effects of aHSCT in MS.

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“…CD161 is expressed on natural killer (NK) cells and subpopulations of T lymphocytes, such as invariant natural killer T cells (iNKT), CD4 + CD161 + T cells, and CD8 + CD161 + T cells [62]. These cells may play significant roles in tumor development [63], and may regulate the immune response in the tumor microenvironment [64].…”

Section: Discussionmentioning

confidence: 99%

Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan

Lee

Fang

et al. 2021

Cancers

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Mounting molecular evidence supports Epstein–Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. 19%). Furthermore, most of the EBER signals detected using in situ hybridization were localized to the nuclei of tumor-infiltrating lymphocytes. In multivariate analysis, EBV DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression (assessed using immunohistochemistry) were identified as independent risk factors for LSCC. Furthermore, five-year local recurrence and disease-free survival rates were 34% and 58%, respectively, with a high EBER signal and low CD3 expression independently predicting five-year local recurrence and disease-free survival. Our comprehensive profiling data accurately identified patients at risk for LSCC development, local recurrence, or disease-free survival. The information obtained in this study improves our understanding of EBV infection in LSCC, and may guide precision medicine for patients with LSCC.

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CD8+CD161+ T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential

Cited by 65 publications

References 82 publications

A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint

A Pan-Cancer Analysis of CD161, a Potential New Immune Checkpoint

NK Cells and Innate-Like T Cells After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan

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