Subtyping of head and neck squamous cell cancers based on immune signatures

Song, Dandan; Lyu, Haoyu; Feng, Qiushi; Luo, Jiangti; Li, Lin; Wang, Qianqian

doi:10.1016/j.intimp.2021.108007

Cited by 9 publications

(13 citation statements)

References 36 publications

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“…Song et al. ( 20 ) reported that COL11A1 more frequently mutated in head and neck cancer patients with high immunity, consistent with our results. Wu et al.…”

Section: Discussionsupporting

confidence: 93%

“…COL11A1 encodes a chain of type XI collagen, which locates in the extracellular matrix, and is up-regulated in various cancers (19). Song et al (20) reported that COL11A1 more frequently mutated in head and neck cancer patients with high immunity, consistent with our results. Wu et al (21) found that COL11A1 activated cancerassociated fibroblasts by modulating TGF-b3 through the NF-kB/IGFBP2 axis.…”

Section: Discussionsupporting

confidence: 91%

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Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis

Song

Yang

et al. 2022

Front. Immunol.

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BackgroundLaryngeal squamous cell carcinoma (LSCC) is one of the world’s most common head and neck cancer. However, the immune infiltration phenotypes of LSCC have not been well investigated.MethodsThe multi-omics data of LSCC were obtained from the TCGA (n=111) and GEO (n=57) datasets. The infiltrations of the 24 immune cell populations were calculated using the GSVA method. Then LSCC samples with different immune cell infiltrating patterns were clustered, and the multi-omics differences were investigated.ResultsPatients were clustered into the high-infiltration and low-infiltration groups. The infiltration scores of most immune cells were higher in the high-infiltration group. Patients with high-infiltration phenotype have high N and TNM stages but better survival, as well as less mutated COL11A1 and MUC17. Common targets of immunotherapies such as PD1, PDL1, LAG3, and CTLA4 were significantly up-regulated in the high-infiltration group. The differentially expressed genes were mainly enriched in several immune-related GOs and KEGG pathways. Based on the genes, miRNAs, and lncRNAs differentially expressed in both the TCGA and GEO cohorts, we built a ceRNA network, in which BTN3A1, CCR1, miR-149-5p, and so on, located at the center. A predictive model was also constructed to calculate a patient’s immune infiltration phenotype using 16 genes’ expression values, showing excellent accuracy and specificity in the TCGA and GEO cohorts.ConclusionsIn this study, the immune infiltration phenotypes of LSCC and the corresponding multi-omics differences were explored. Our model might be valuable to predicting immunotherapy’s outcome.

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“…Song et al. ( 20 ) reported that COL11A1 more frequently mutated in head and neck cancer patients with high immunity, consistent with our results. Wu et al.…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis

Song

Yang

et al. 2022

Front. Immunol.

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“…Furthermore, the limited response could be partly due to additional upregulation of other immune-suppressive immune checkpoint molecules on HNSCCs, as has already been demonstrated for the herpesvirus entry mediator (HVEM) in breast cancer [25]. However, the overall knowledge about the expression of key immune checkpoint molecules in addition to PD-L1 in HNSCCs following RT is scarce [26], and thus is in the focus of our here presented examinations. Additionally, agonists targeting the inducible T cell co-stimulator (ICOS, CD278) are currently under clinical investigation also for HNSCC, with the aim to, synergistically with anti-PD-1, inhibit the suppressive activity of regulatory T cells and to potentiate the anti-tumor activity of effector T cells [27].…”

Section: Introductionmentioning

confidence: 92%

Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells

Wimmer¹,

Deloch²,

Häder³

et al. 2021

IJMS

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While the treatment of squamous cell carcinoma of the head and neck (HNSCC) with radiotherapy (RT) is complemented more and more by immunotherapy in clinical trials, little is known about the impact of the human papillomavirus (HPV) status or the applied RT scheme on the immune phenotype of the tumor cells. Therefore, we aimed to examine the impact of the HPV status of four human HNSCC cell lines on cell death and the expression of immune checkpoint molecules (ICMs) after RT with either hypofractionation irradiation (5x3.0Gy) or a high single dose (1x19.3Gy) via multicolor flow cytometry and quantitative PCR at an early time point after therapy. In our study, 5x3.0Gy RT induced high numbers of early and late apoptotic cells independent of the HPV status, but necrosis was only increased in the HPV-positive UM-Scc-47 cells. Generally, the immune stimulatory ICMs (CD70, CD137-L, ICOS-L) were less affected by RT compared to the immune suppressive ones (PD-L1, PD-L2, and the herpesvirus entry mediator (HVEM)). A significant higher surface expression of the analyzed ICMs was found after hypofractionated RT compared to a single high dose; however, regardless of the HPV status, with the exception of ICOS-L. Here, HPV-positive HNSCC tumor cells showed a stronger response to 5x3.0Gy than HPV-negative ones. On the RNA level, only minor alterations of ICMs were observed following RT, with the exception of the HPV negative cell line CAL33 treated with 5x3.0Gy, where PD-L2, HVEM and CD70 were significantly increased. We conclude that the HPV status may not distinctly predict immunological responses following RT, and thus cannot be used as a single predictive marker for therapy responses in HNSCC. In contrast, the patient-specific individual expression of ICMs following RT is preferable for the targeted patient selection for immune therapy directed against distinct ICM.

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“…A recent study analyzing immune signatures in HNSCC proposed three different subtypes of these malignancies Immunity-H, -M, and -L (high, medium, and low, respectively). The first one was characterized by increased immune and stromal infiltration, low tumor purity, low stemness, as well as intratumor heterogeneity, genomic stability, and favorable prognosis in contrast to the immunity-L subtype [ 120 ]. These findings seem to support our obtained results.…”

Section: Discussionmentioning

confidence: 99%

“…The Immunity-H subtype is associated with a higher rate of HPV infections in comparison to the Immunity-L subtype (40% vs. 22%) [ 120 ]. It has been proven that HPV-positive patients with oropharyngeal squamous cell carcinoma (OPSCC) who are current smokers or have tobacco use history tend to have a dysregulated ncRNA expression landscape, including downregulation of miR-154-5p , and unfavorable treatment outcomes [ 121 ].…”

Section: Discussionmentioning

confidence: 99%

miR-154 Influences HNSCC Development and Progression through Regulation of the Epithelial-to-Mesenchymal Transition Process and Could Be Used as a Potential Biomarker

et al. 2021

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MicroRNAs and their role in cancer have been extensively studied for the past decade. Here, we analyzed the biological role and diagnostic potential of miR-154-5p and miR-154-3p in head and neck squamous cell carcinoma (HNSCC). miRNA expression analyses were performed using The Cancer Genome Atlas (TCGA) data accessed from cBioPortal, UALCAN, Santa Cruz University, and Gene Expression Omnibus (GEO). The expression data were correlated with clinicopathological parameters. The functional enrichment was assessed with Gene Set Enrichment Analysis (GSEA). The immunological profiles were assessed using the ESTIMATE tool and RNAseq data from TCGA. All statistical analyses were performed with GraphPad Prism and Statistica. The study showed that both miR-154-5p and miR-154-3p were downregulated in the HNSCC samples and their expression levels correlated with tumor localization, overall survival, cancer stage, tumor grade, and HPV p16 status. GSEA indicated that individuals with the increased levels of miR-154 had upregulated AKT-MTOR, CYCLIN D1, KRAS, EIF4E, RB, ATM, and EMT gene sets. Finally, the elevated miR-154 expression correlated with better immune response. This study showed that miR-154 is highly involved in HNSCC pathogenesis, invasion, and immune response. The implementation of miR-154 as a biomarker may improve the effectiveness of HNSCC treatment.

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Subtyping of head and neck squamous cell cancers based on immune signatures

Cited by 9 publications

References 36 publications

Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis

Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis

Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells

miR-154 Influences HNSCC Development and Progression through Regulation of the Epithelial-to-Mesenchymal Transition Process and Could Be Used as a Potential Biomarker

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