How Natural Killer Cell Receptors Stick to Cell–Cell Adhesion Proteins

Karade, S.S.; Mariuzza, Roy A.

doi:10.1016/j.str.2019.01.007

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Tumor cells achieve tumor infiltration by secreting various proteolytic enzymes that disrupt cell–cell adhesion 67 . In addition, cell adhesion molecules are involved in regulating NK cell function 68 . Comparing the differences in somatic mutations, we found that the frequency of mutations in GNA11 and BAP1 was higher in the high-risk.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Zhao,

Yu,

Song

2024

Sci Rep

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Uveal melanoma (UVM) is the most common primary tumor in adult human eyes. Costimulatory molecules (CMs) are important in maintaining T cell biological functions and regulating immune responses. To investigate the role of CMs in UVM and exploit prognostic signature by bioinformatics analysis. This study aimed to identify and validate a CMs associated signature and investigate its role in the progression and prognosis of UVM. The expression profile data of training cohort and validation cohort were downloaded from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) dataset. 60 CM genes were identified, and 34 genes were associated with prognosis by univariate Cox regression. A prognostic signature was established with six CM genes. Further, high- and low-risk groups were divided by the median, and Kaplan–Meier (K-M) curves indicated that high-risk patients presented a poorer prognosis. We analyzed the correlation of gender, age, stage, and risk score on prognosis by univariate and multivariate regression analysis. We found that risk score was the only risk factor for prognosis. Through the integration of the tumor immune microenvironment (TIME), it was found that the high-risk group presented more immune cell infiltration and expression of immune checkpoints and obtained higher immune scores. Enrichment analysis of the biological functions of the two groups revealed that the differential parts were mainly related to cell–cell adhesion, regulation of T-cell activation, and cytokine–cytokine receptor interaction. No differences in tumor mutation burden (TMB) were found between the two groups. GNA11 and BAP1 have higher mutation frequencies in high-risk patients. Finally, based on the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) dataset, drug sensitivity analysis found that high-risk patients may be potential beneficiaries of the treatment of crizotinib or temozolomide. Taken together, our CM-related prognostic signature is a reliable biomarker that may provide ideas for future treatments for the disease.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Zhao,

Yu,

Song

2024

Sci Rep

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“…The structural basis for the CD96-CD155 interaction involves the “ancillary key” motif that is critical for CD155 recognition; moreover, CD96 and CD155 interact via the “lock-and-key” docking mode (79). However, surprisingly, a comparison between three anti-CD96 mAbs, including two that block the CD96-CD155 interaction (3.3 and 6A6) and one that does not block this interaction (8B10), revealed that although the two blocking mAbs showed higher potency than the non-blocking mAb in the control of metastases, it was not necessary to block the CD96-CD155 interaction to promote NK cell antimetastatic functions (80, 81). In contrast, another study using a transgenic mouse model of resectable pancreatic ductal adenocarcinoma showed that a mAb targeting the CD96-CD155 interaction (6A6) significantly reduced distant metastases, while a mAb that did not target the CD96-CD155 interaction (8B10) showed no effect on the frequency of metastases (82).…”

Section: Immunoglobulin Superfamilymentioning

confidence: 99%

The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy

Sun

2019

Front. Immunol.

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Checkpoint immunotherapy that targets inhibitory receptors of T cells, thereby reversing the functional exhaustion of T cells, marks a breakthrough in anticancer therapy. The success of T cell-directed checkpoint inhibitors of CTLA-4 and PD-1/PD-L1 has opened a new approach for cancer immunotherapy and resulted in extensive research on immune checkpoints. However, it is only in recent years that research on NK cell exhaustion and potential checkpoints impacting NK cells has become popular. NK cells, as the major player in innate immunity, are critical for immune surveillance, particularly the control of metastasis and hematological cancers. The balance between activating and inhibitory signals fine tunes the activation and effector functions of NK cells, and transformed cells modulate NK cells by upregulating negative signaling that “exhausts” NK cells. Exhausted NK cells with excessive expression of inhibitory receptors (checkpoint molecules) are impaired in the recognition of tumor cells as well as antitumor cytotoxicity and cytokine secretion. Therefore, an understanding of the potential checkpoint molecules involved in NK cell exhaustion is particularly important in terms of NK cell-targeted cancer immunotherapy. In this review, we summarize recent advances in NK cell checkpoint inhibitors and their progress in clinical trials. Moreover, we highlight some of the latest findings in fundamental NK cell receptor biology and propose potential NK cell checkpoint molecules for future immunotherapeutic applications.

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Eczema Herpeticum: Clinical Insights and Pathogenesis Hypotheses on Basolateral Adhesion Proteins

Martínez-Ortega,

Franco González

2024

Cureus

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How Natural Killer Cell Receptors Stick to Cell–Cell Adhesion Proteins

Cited by 3 publications

References 10 publications

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy

Eczema Herpeticum: Clinical Insights and Pathogenesis Hypotheses on Basolateral Adhesion Proteins

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