Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival

Yu, Hanry; Tang, Huiwen; Franceschi, Debora; Mujagond, Prabhakar; Acharya, Aneesha; Deng, Yupei; Lethaus, Bernd; Savkovic, Vuk; Zimmerer, Rüdiger; Ziebolz, Dirk; Li, Simin; Schmalz, Gerhard

doi:10.3389/fmed.2021.759605

Cited by 6 publications

(11 citation statements)

References 62 publications

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“…Combining targeted medicine that is aimed at the microenvironment for cancer with conventional treatment such as chemotherapy and radiotherapy might enhance tumor patient’s efficacy in the practical field. Researchers anticipate the development of additional therapies to tackle checkpoint components would enhance the clinical results for patients and eventually lead to cancer eradication [ 24 , 25 , 31 ]. The majority of findings for elderly and ccRCC patients, whether in localized or distant areas during the ICI and non-ICI era, are still in their early stages [ 32 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…We included coding genes (19,658 genes) from fragments per kilobase of exon per million mapped (FPKM). In the study of gene expression, these were matched with the ICI genes that were obtained from new ICI databases (the checkpoint therapeutic target database (CKTTD) and recently published new ICI genes list) [ 24 , 25 ]. For validation of our gene signature, we used the gene expression profile of 604 ccRCC patients from the GEO database (GSE167093) [ 26 ].…”

Section: Patient’s Methods and Materialsmentioning

confidence: 99%

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Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study

Al-Danakh

Safi²,

Alradhi³

et al. 2022

Cells

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Background: It is anticipated that there will be a large rise in the number of tumor diagnoses and mortality in those aged 65 and older over the course of upcoming decades. Immune checkpoint inhibitors, often known as ICIs, boost immune system activity by selectively targeting ICI genes. On the other hand, old age may be connected with unfavorable results. Methods: The Cancer Genome Atlas (TCGA) provided gene expression data from ccRCC tissue and key clinical variables. ICI gene databases were applied and verified using the GEO database. Results: We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival. Then, by utilizing a new nomogram method, the TNFSF15 gene and age predicting values were estimated at one, three, and five years (85%, 81%, and 81%), respectively, and our age-related risk score was significant even after multivariable analysis (HR = 1.518, p = 0.009, CI = 1.1102.076). TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001). A negative connection between age and the TNFSF15 gene expression was discovered by correlation analysis (p = 0.0001). The verification of the gene by utilizing GEO (GSE167093) with 604 patients was obtained as external validation that showed significant differences in the TNFSF15 gene between young and elderly patients (p = 0.007). Additionally, the protein–protein interactions of the TNFSF15 gene with other ICI genes and aging-related genes was determined. In addition, the TNFSF15 expression was significantly correlated with pathological stages (p = 0.018). Furthermore, it was discovered that the biological processes of senescence, cellular senescence, the immune system, and many immune cell infiltration and immune function types are all closely tied. Conclusions: Along with the risk score evaluation, the ICI gene TNFSF15 was identified as a tumor suppressor gene related to inequalities in age survival and is associated with pathological stages and different immunity statuses. The aging responses of ccRCC patients and related gene expression need further investigation in order to identify potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Patient’s Methods and Materialsmentioning

confidence: 99%

Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study

Al-Danakh

Safi²,

Alradhi³

et al. 2022

Cells

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“…Survival analysis showed that most ICs, including BTLA, were significantly associated with OS. Combinations such as low PD-L1/ low BTLA and high CD8alpha/ low BTLA were predictive of a favorable prognosis in OSCC [ 84 ]. Similarly, Weber et al performed a comparative analysis of IC expression in OSCC.…”

Section: Btla In Cancermentioning

confidence: 99%

BTLA biology in cancer: from bench discoveries to clinical potentials

Andrzejczak,

Karabon

2024

Biomark Res

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Immune checkpoints play a critical role in maintaining the delicate balance of immune activation in order to prevent potential harm caused by excessive activation, autoimmunity, or tissue damage. B and T lymphocyte attenuator (BTLA) is one of crucial checkpoint, regulating stimulatory and inhibitory signals in immune responses. Its interaction with the herpes virus entry mediator (HVEM) plays an essential role in negatively regulating immune responses, thereby preserving immune homeostasis. In cancer, abnormal cells evade immune surveillance by exploiting checkpoints like BTLA. Upregulated BTLA expression is linked to impaired anti-tumor immunity and unfavorable disease outcomes. In preclinical studies, BTLA-targeted therapies have shown improved treatment outcomes and enhanced antitumor immunity. This review aims to provide an in-depth understanding of BTLA’s biology, its role in various cancers, and its potential as a prognostic factor. Additionally, it explores the latest research on BTLA blockade in cancer immunotherapy, offering hope for more effective cancer treatments.

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“…JUN-dependent immune checkpoint expression was inhibited by blocking CDK1/2/5 in pancreatic cancer in response to interferon gamma [ 11 ]. Targeting immune checkpoints by blocking co-inhibitory molecules or activating co-stimulatory molecules has emerged as one of the important options in cancer treatment [ 18 ]. Microsatellite instability (MSI) and tumor mutational burden (TMB) function as predictive biomarkers for favorable outcomes of cancer immunotherapy [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

An Integrative Human Pan-Cancer Analysis of Cyclin-Dependent Kinase 1 (CDK1)

Liu

2022

Cancers

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Cyclin-dependent kinase 1 (CDK1) is essential for cell division by regulating the G2/M phase and mitosis. CDK1 overexpression can also promote the development and progression of a variety of cancers. However, the significance of CDK1 in the formation, progression, and prognosis of human pan-cancer remains unclear. In the present study, we used The Cancer Genome Atlas database, Clinical Proteomic Tumor Analysis Consortium, Human Protein Atlas, Genotype-Tissue Expression, and other well-established databases to comprehensively examine CDK1 genetic alterations and gene/protein expression in various cancers and their relationships with the prognosis, immune reactivities, and clinical outcomes for 33 tumor types. Gene set enrichment analysis was also conducted to examine the potential mechanisms of CDK1 in tumorigenesis. The data showed that CDK1 mutation was frequently present in multiple tumors. CDK1 expression was significantly increased in various types of tumors as compared with normal tissues and was associated with poor overall and disease-free survival. In addition, CDK1 expression was significantly correlated with oncogenic genes, proteins, cellular components, myeloid-derived suppressor cell infiltration, ESTMATEScore, and signaling pathways associated with tumor development and progression and tumor microenvironments. These data indicate that CDK1 could serve as a promising biomarker for predicting tumor prognosis and a potential target for cancer treatment.

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Immune Checkpoint Gene Expression Profiling Identifies Programmed Cell Death Ligand-1 Centered Immunologic Subtypes of Oral and Squamous Cell Carcinoma With Favorable Survival

Cited by 6 publications

References 62 publications

Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study

Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study

BTLA biology in cancer: from bench discoveries to clinical potentials

An Integrative Human Pan-Cancer Analysis of Cyclin-Dependent Kinase 1 (CDK1)

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