Project description:The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade has resulted in a variety of preclinical investigations, yet the mechanism of action in humans remains unknown. We used scRNAsequencing and multi-spectral spatial imaging to elucidate the tumor immune microenvironment and correlates to response to a a unique open-label phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC)
Project description:Afatinib is a pan-HER inhibitor that improved progression-free-survival (PFS) in recurrent HNSCC versus methotrexate: median PFS 2.6 versus 1.7 months (LUX H&N 1 trial). This study is a translational research linked to EORTC 90111 afatinib trial, an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve HNSCC patients selected for primary curative surgery were randomized (5:1 ratio) to receive Afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumour biopsies, FDG/PET, and MRI were performed at diagnosis and at surgery. The primary end point was metabolic FDG-PET/CT response, defined according to EORTC guidelines.
Project description:The EORTC-90111-24111 window study included treatment-naïve patients with primary HNSCC receiving afatinib versus no preoperative treatment. We found that treated patients had an increase in tumor CD3+ density and CD3+ and CD8+ T-cell infiltration compared to control patients. Afatinib- exposed tumor had upregulation of gene expression signatures predictive of response to PD-1 blockade. Also, we observed two clusters among treated patients. Cluster 1 showed a higher expression of markers and gene sets implicated in epithelial-to-mesenchymal transition and cancer-associated fibroblasts activation after afatinib compared to cluster 2 and controls. These results open perspectives to overcome resistance mechanisms to anti-HER therapy and to potentiate the activity of immune checkpoint inhibitors.
Project description:Post-operative radiation therapy (PORT) is the standard treatment for patients with head and neck squamous cell carcinoma (HNSCC) having adverse pathological features. Despite PORT, many patients develop relapse causing morbidity and mortality. These specimens are from a high-risk cohort of such patients treated by PORT and are being used to develop gene signatures for therapeutic response.
Project description:MiRNA expression profiles were successfully examined through expression profiling of a total of 656 miRNAs between 2 head and neck squamous cell carcinoma (HNSCC) tissues (C) and their paired adjacent normal mucousal tissues (AN). In the study presented here, 2 head and neck squamous cell carcinoma (HNSCC) tissues (C) and their paired adjacent normal mucousal tissues (AN) were examined by miRNA array
Project description:To test whether HIF-1a can directly induce Timp1 expression in periosteal cells at the pre-invasive stage of head and neck squamous cell carcinoma (HNSCC), we performed Chromatin immunoprecipitation followed by sequencing (ChIP–seq) on periosteal cells derived from the pre-invasive stage of a mouse HNSCC bone invasion model by using antibodies to acetylated histone H3 Lys27 (H3K27ac), H3K4me3 and HIF-1α.
Project description:This study represents a proteomic resource for HNSCC and SQCLC with quantitative protein expression data for 7800 proteins and provides a proteomic diagnostic signature for classification for undetermined secondary lung tumors in HNSCC patients. By quantitative mass-spectrometry-based proteomics, we characterized a cohort of 63 squamous cell carcinomas of the lung (SQCLC), 49 of the head and neck region (HNSCC) and 51 HNSCC-correlated lung tumors with squamous cell histology that evolved in the course of the disease.
Project description:Head and neck squamous cell carcinomas (HNSCC) driven by human papillomavirus (HPV) generally have a more favourable prognosis. We hypothesized that HPV-positive HNSCC may be identified based on a miRNA signature according to their specific molecular pathogenesis and are characterized by a unique transcriptome compared to HPV-negative HNSCC. We characterized the miRNA-expression patterns of the tumors from 229 head and neck squamous cell carcinoma patients by Agilent miRNA microarrays in order to define a HPV-predicting miRNA signature.
Project description:To determine the differential expression of KRAS-variant HNSCC (head and neck squamous cell carcinoma) cell lines. Total RNA collected from a panel of HNSCC cell lines.
