Dataset Information

Multi-Omics Data Analyses Identify B7-H3 as a Novel Prognostic Biomarker and Predict Response to Immune Checkpoint Blockade in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: B7 homolog 3 (B7-H3) is a recently found superfamily B7 molecule and therefore has significant involvement in immunological regulation. However, the relationships of B7-H3 expression with the tumor microenvironment (TME), response to immunotherapy, and prognosis in head and neck squamous cell carcinoma (HNSCC) are still unknown. In the present analysis, we determined B7-H3 as a novel biomarker that predicts the prognosis and response to immunotherapy in HNSCC. B7-H3 expression is enhanced in HNSCC compared to normal sample and is stably expressed in HNSCC cell line. Besides, high B7-H3 expression is correlated with a dismal prognosis and resistance to immunotherapy and contributes to an immunosuppressive microenvironment. Moreover, single-cell RNA sequencing (scRNA-seq) analysis shows that B7-H3 is mainly expressed in the stromal as well as malignant cells. In conclusion, the study provides insight in understanding the prognostic value of B7-H3 in HNSCC and highlights its involvement in promoting the immunosuppressive microenvironment, which presents an attractive strategy for antibody-based immunotherapy.

SUBMITTER: Lin W

PROVIDER: S-EPMC8524082 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Multi-Omics Data Analyses Identify B7-H3 as a Novel Prognostic Biomarker and Predict Response to Immune Checkpoint Blockade in Head and Neck Squamous Cell Carcinoma.

Lin Wanzun W Xu Yanyan Y Gao Jing J Zhang Haojiong H Sun Yun Y Qiu Xianxin X Huang Qingting Q Kong Lin L Lu Jiade J JJ

Frontiers in immunology 20211005

B7 homolog 3 (B7-H3) is a recently found superfamily B7 molecule and therefore has significant involvement in immunological regulation. However, the relationships of B7-H3 expression with the tumor microenvironment (TME), response to immunotherapy, and prognosis in head and neck squamous cell carcinoma (HNSCC) are still unknown. In the present analysis, we determined B7-H3 as a novel biomarker that predicts the prognosis and response to immunotherapy in HNSCC. B7-H3 expression is enhanced in HNS ...[more]

PMID: 34675936

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Project description:The success of immune checkpoint receptor blockade has brought exciting promises for the treatment of head and neck squamous cell carcinoma (HNSCC). While patients who respond to checkpoint inhibitors tend to develop a durable response, <15% of patients with HNSCC respond to immune checkpoint inhibitors, underscoring the critical need to alleviate cancer resistance to immunotherapy. Major advances have been made to elucidate the intrinsic and adaptive resistance mechanisms to immunotherapy. Central genomic events in HNSCC have been found to possess previously unknown roles in suppressing immune sensing. Such inhibitory function affects both the innate and adaptive arms of tumor-specific immunity. While checkpoint blockade effectively reinvigorates adaptive T-cell responses, additional targeting of the oncogenic inhibitors of innate immune sensing likely informs a novel and potent strategy for immune priming. This review discusses the recent advances on the identification of key HNSCC oncogenes that impair antitumor immunity and emerging immune-priming approaches that sensitize poorly immunogenic HNSCCs to checkpoint blockade. These approaches include but are not limited to cancer vaccine systems utilizing novel type I interferon agonists as immune adjuvants, radiation, DNA damage-inducing agents, and metabolic reprogramming. The goal of these multipronged approaches is to expand tumor-specific effector T-cells, break checkpoint receptor-mediated tolerance, and metabolically support sustained T-cell activation. The translation of therapeutics that reverses oncogenic inhibition of immune sensing requires thorough characterization of the HNSCC regulators of innate immune sensors, development of additional immunocompetent HNSCC mouse models, as well as engineering of more robust immune adjuvant delivery systems. Built on the success of checkpoint blockade, validation of novel immune-priming approaches holds key promises to expand the pool of responders to immunotherapy.

Project description:(Purpose) Previous studies have pointed out the significance of IgG Fc binding protein (FCGBP) in carcinogenesis, cancer progression, and tumor immunity in certain malignancies. However, its prognostic values, molecular interaction, and immune characteristics in the head and neck squamous cell carcinoma (HNSC) remained unclear. (Methods) To evaluate the potential role of the FCGBP gene, we used GEPIA2 and UALCAN platforms to explore the differential levels, survivals, and genetic alteration through cBioPortal (based on The Cancer Genome Atlas dataset). STRING, GeneMania, and TIMER2.0 identified the interacting networks. LinkedOmics performed Gene enrichment analysis, and TISIDB and TIMER2.0 evaluated the role of FCGBP in the tumor microenvironment. (Results) The expression level of FCGBP is lower in cancer tissues. A high FCGBP level is significantly associated with better overall- and disease-specific-survivals, regardless of human papillomavirus infection. Low FCGBP levels correlated to a higher tumor protein p53 (TP53) mutation rate (p = 0.018). FCGBP alteration significantly co-occurred with that of TP53 (q = 0.037). Interacting networks revealed a significant association between FGFBP and trefoil factor 3 (TFF3), a novel prognostic marker in various cancers, at transcriptional and translational levels. Enrichment analyses identified that the top gene sets predominantly related to immune and inflammatory responses. Further investigation found that the FCGBP mRNA level positively correlated to the infiltration rates of B cells, Th17/CD8+ T lymphocytes, T helper follicular cells, mast cells, and expression levels of various immune molecules and immune checkpoints in HNSC. (Conclusions) We found that the FCGBP mRNA level negatively correlated to TP53 mutation status while positively correlated to the TFF3 level. Additionally, FCGBP may regulate the tumor microenvironment. These findings support the FCGBP as a potential biomarker to estimate HNSC prognoses.

Project description:PurposeImmunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs (lncRNAs) impact every step of cancer immunity. Therefore, reliable immune-lncRNAs able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management.MethodsIn the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Atlas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, and chemotherapeutic and immunotherapeutic efficacy between two groups.ResultsIn our study, we identified 256 Deir-lncRNAs in HNSCC. A total of 18 Deir-lncRNA pairs (consisting of 35 Deir-lncRNAs) were used to construct a risk model significantly associated with survival of HNSCC. Cox proportional hazard regression analysis confirmed that our risk model could be served as an independent prognostic indicator. Besides, HNSCC patients with low-risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity.ConclusionOur risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

Dataset Information

Multi-Omics Data Analyses Identify B7-H3 as a Novel Prognostic Biomarker and Predict Response to Immune Checkpoint Blockade in Head and Neck Squamous Cell Carcinoma.

Publications

Multi-Omics Data Analyses Identify B7-H3 as a Novel Prognostic Biomarker and Predict Response to Immune Checkpoint Blockade in Head and Neck Squamous Cell Carcinoma.

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