Identification of a Costimulatory Molecule Gene Signature to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

Aye, Ling; Song, Xiaole; Yang, Jingyi; Hu, Li; Sun, Xicai; Zhou, Jiaju; Liu, Quan; Yu, Hongmeng; Wang, Dehui

doi:10.3389/fcell.2021.695533

Cited by 12 publications

(13 citation statements)

References 58 publications

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“…Immunotherapy is a therapy with potentially profound efficiency, but not all patients experience this, and this underlines the importance of choosing the correct patients as candidates for immunotherapy [ 41 ]. It is possible to use information gathered along many lines in order to predict patient response to immunotherapy [ 42 ], but simpler approaches are easier to use everywhere. To study the TIL Foxp3 level in HNSCC patients eligible for immunotherapy to determine treatment result could be part of a future simple suggestion in order to better aim such treatment.…”

Section: Discussionmentioning

confidence: 99%

Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients

et al. 2022

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Oropharynx squamous cell carcinoma (OPSCC) is of special interest because human papilloma virus (HPV) and/or smoking cause this disease. Influxes of inflammatory cells into such tumors are known to vary with prognoses. Aims: To study whether the density of tumor-infiltrating T lymphocytes and tumor-infiltrating macrophages predicted general 20-year overall survival (OS), as well as OS with only disease-specific survival (DSS) patients included. Methods: Biopsies from patients treated for OPSCC (n = 180) were stained by immunohistochemistry and the tumor cell macrophage (CD68), pan T lymphocytes (CD3), and regulatory T lymphocytes (Foxp3) densities were determined. The HE-determined percentage of matured tumor cells and the rate of invasion were calculated, and stromal desmoplasia were performed. Tumor HPV presence was studied by PCR. Twenty-year OS and five-year DSS patients were determined. Results: Tumor HPV status strongly predicted survival. High tumor infiltration of CD3, Foxp3 and CD68-positive cells predicted better twenty-year OS, with and without HPV stratification. Foxp3 and CD68 levels predicted OS, and 20-year among DSS patients, primarily among HPV(+) patients. Tumor HE-derived variables did not predict such survival. Conclusions: Tumor HPV status, level of Foxp3 tumor-infiltrating lymphocytes and CD68 tumor-infiltrating macrophages predicted up to 20-year OS of both all patients and disease-specific survived patients.

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Section: Discussionmentioning

confidence: 99%

Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients

et al. 2022

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“…PD1 and cytotoxic T lymphocyte antigen 4 (CTLA4), both members of the CD28 family, are the focus of current immunotherapy research [ 12 ]. The costimulatory molecule had been used for the prediction of immunotherapy response and prognosis in several tumors [ 13 , 14 ]. Nonetheless, the value of costimulatory molecules in the prognosis and immunotherapy in HCC has not been fully explored.…”

Section: Discussionmentioning

confidence: 99%

Development of a Costimulatory Molecule Signature to Predict Prognosis, Immune Landscape, and Response to Immune Therapy for Hepatocellular Carcinoma

Zhou

Liu

et al. 2022

Disease Markers

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This work was aimed at investigating the predictive value on prognosis, response to immunotherapy, and association with the immune landscape of costimulatory molecules in HCC patients. We acquired the clinicopathological information and gene expression of HCC patients from public available database (TCGA and GEO). The prognostic model in TCGA database was established with LASSO regression and Cox regression analysis. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, the enrichment analysis was implemented for analyzing the biological function and associated pathways. Immune microenvironment, immune escape, immune therapy, and tumor mutation were analyzed between both risk groups. TNFRSF4, the critical costimulatory molecule, was chosen for the in-depth investigation in vitro experiments. A novel risk signature based on 8 costimulatory molecules associated with prognosis was constructed from TCGA and proved in the database of GEO. The ROC and Kaplan-Meier curves confirmed that this risk model has good predictive accuracy. Our functional analysis demonstrated costimulatory molecular genes might associate with immune-related functions and pathways. Statistical differences were not shown between both groups, in the aspect of immune landscape, response to immune therapy, and tumor mutation. Knocking down TNFRSF4 expression significantly reduced the proliferation ability and increased the apoptosis ability. On the basis of the costimulatory molecule expression in HCC, a novel risk model was constructed and had an excellent value to predict prognosis, immune microenvironment, and response to immune therapy. TNFRSF4 was identified as an underlying oncogene in HCC and deserves further exploration.

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“…There were no significantly differences in clinical characteristics between two sets (Table 1 ). Furthermore, a total of sixty costimulatory molecules genes (CMGs) were collected from prior reviews [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

Identification and validation a costimulatory molecule gene signature to predict the prognosis and immunotherapy response for hepatocellular carcinoma

Liu

et al. 2022

Cancer Cell Int

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Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Costimulatory molecules have been proven to be the foundation of immunotherapy. However, the potential roles of costimulatory molecule genes (CMGs) in HCC remain unclear. Our study is aimed to develop a costimulatory molecule-related gene signature that could evaluate the prognosis of HCC patients. Methods Based on The Cancer Gene Atlas (TCGA) database, univariate Cox regression analysis was applied in CMGs to identify prognosis-related CMGs. Consensus clustering analysis was performed to stratify HCC patients into different subtypes and compared them in OS. Subsequently, the LASSO Cox regression analysis was performed to construct the CMGs-related prognostic signature and Kaplan–Meier survival curves as well as ROC curve were used to validate the predictive capability. Then we explored the correlations of the risk signature with tumor-infiltrating immune cells, tumor mutation burden (TMB) and response to immunotherapy. The expression levels of prognosis-related CMGs were validated based on qRT-PCR and Human Protein Atlas (HPA) databases. Results All HCC patients were classified into two clusters based on 11 CMGs with prognosis values and cluster 2 correlated with a poorer prognosis. Next, a prognostic signature of six CMGs was constructed, which was an independent risk factor for HCC patients. Patients with low-risk score were associated with better prognosis. The correlation analysis showed that the risk signature could predict the infiltration of immune cells and immune status of the immune microenvironment in HCC. The qRT-PCR and immunohistochemical results indicated six CMGs with differential expression in HCC tissues and normal tissues. Conclusion In conclusion, our CMGs-related risk signature could be used as a prediction tool in survival assessment and immunotherapy for HCC patients.

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Identification of a Costimulatory Molecule Gene Signature to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

Cited by 12 publications

References 58 publications

Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients

Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients

Development of a Costimulatory Molecule Signature to Predict Prognosis, Immune Landscape, and Response to Immune Therapy for Hepatocellular Carcinoma

Identification and validation a costimulatory molecule gene signature to predict the prognosis and immunotherapy response for hepatocellular carcinoma

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