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

Zhou, Xiaohan; Du, Jie; Liu, Chengdong; Zeng, Hanyi; Chen, Yuting; Liu, Li; Wu, De‐Hua

doi:10.3389/fimmu.2021.688215

Cited by 48 publications

(48 citation statements)

References 27 publications

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“…CD161, as the marker of GBM tumor infiltrating lymphocytes, is widely expressed on the plasma membrane surface of NK cells, CD8 + and CD4 + T cells [ 207 ], binding to the ligand CLEC2/Lectin like transcript-1(LLT1) mainly expressed in GBM myeloid cells [ 208 ]. Previous studies have confirmed that CD161 directly interacts with intracellular acid sphingomyelinase to regulate Akt signaling pathway and then inhibits activity of NK cell.…”

Section: Glioblastomamentioning

confidence: 99%

Glioma targeted therapy: insight into future of molecular approaches

et al. 2022

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Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.

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Section: Glioblastomamentioning

confidence: 99%

Glioma targeted therapy: insight into future of molecular approaches

et al. 2022

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“…In this study, KLRB1 was found to be the gene most frequently associated with favorable clinical outcome in ~18 000 human tumors across 39 malignancies. Further analysis of KLRB1 RNA expression and clinical data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) indicate that it is upregulated in most human cancers but also downregulated in others (98).…”

Section: Expression Of Cd161 Is Associated With Good Prognosis In Mos...mentioning

confidence: 99%

LLT1-CD161 Interaction in Cancer: Promises and Challenges

et al. 2022

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The success of immune checkpoint therapy in cancer has changed our way of thinking, promoting the design of future cancer treatments that places the immune system at the center stage. The knowledge gained on immune regulation and tolerance helped the identification of promising new clinical immune targets. Among them, the lectin-like transcript 1 (LLT1) is the ligand of CD161 (NKR-P1A) receptor expressed on natural killer cells and T cells. LLT1/CD161 interaction modulates immune responses but the exact nature of the signals delivered is still partially resolved. Investigation on the role of LLT1/CD161 interaction has been hampered by the lack of functional homologues in animal models. Also, some studies have been misled by the use of non-specific reagents. Recent studies and meta-analyses of single cell data are bringing new insights into the function of LLT1 and CD161 in human pathology and notably in cancer. The advances made on the characterization of the tumor microenvironment prompt us to integrate LLT1/CD161 interaction into the equation. This review recapitulates the key findings on the expression profile of LLT1 and CD161, their regulation, the role of their interaction in cancer development, and the relevance of targeting LLT1/CD161 interaction.

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“…Although immunotherapy brings new hope to cancer patients, many patients remain insensitive to immunotherapy [18,19]. Some relative researches have proved that the remodeling of TIME by cancer cells pay an emphasis on the resistance to immunotherapy, which to reduce the response of tumor patients to treatment and it may be result in worse survival status [20,21].…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis reveals NUP37 as a prognostic biomarker correlated with the immunosuppressive microenvironment in glioma

Shen

et al. 2022

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Nucleoporin 37 kDa (NUP37), a member of the nucleoporin family, has been reported to regulate the proliferation and apoptosis of several tumor types. However, its role in the tumor immune microenvironment is unclear. Here, we evaluated the expression, methylation, copy number alteration, and prognostic significance of NUP37 using RNA-seq and clinical data from The Cancer Genome Atlas. We observed higher expression of NUP37 in 28 of 29 tumor types, and high NUP37 expression predicted worse survival status of patients in 15 tumors. Using data from the cBioportal database, we described the gene variation of NUP37 in glioma and pancancer. We further assessed the role of NUP37 in the tumor immune microenvironment using immune infiltration data. NUP37 expression was positively associated with the infiltration levels of immunosuppressive cells, such as nTregs, iTregs, and tumor-associated macrophages, and negatively correlated with immune killer cells, such as CD8+ T and NK cells across cancers. Furthermore, NUP37 expression was associated with immune checkpoints and immune regulation-related genes. The half-maximal inhibitory concentrations of anti-cancer drugs were obtained from the Genomics of Drug Sensitivity in the Cancer database. The correlation between half-maximal inhibitory concentration and NUP37 expression was evaluated. The patients with the evaluated expression of NUP37 were resistant to several anti-cancer drugs. These results suggest that NUP37 is a potential oncogene and prognostic biomarker in glioma and pan-cancer. Tumor tissues with high NUP37 expression exist in a relatively immunosuppressive microenvironment and are resistant to several anti-cancer drugs.

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

Cited by 48 publications

References 27 publications

Glioma targeted therapy: insight into future of molecular approaches

Glioma targeted therapy: insight into future of molecular approaches

LLT1-CD161 Interaction in Cancer: Promises and Challenges

Pan-cancer analysis reveals NUP37 as a prognostic biomarker correlated with the immunosuppressive microenvironment in glioma

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