The goal of this project is to characterise the heterogeneity of all cell populations (tumour cells, stromal and immune microenvironment) present in the tumor and their normal (and OPMD) counterparts by scRNAseq in OSCC patients. Additionally, the study will evaluate the effectiveness of non-invasive cytobrushes as a diagnostic tool compared to traditional biopsies.
Epidermoid carcinomas of upper aerodigestive tract are the 8th most common cancers in the world. Worldwide, this represents more than 500.000 cases per year and 20.000 cases per year in France (statistics 2018-2020). Among these cancers, oral squamous cell carcinoma (OSCC) are the most common location, leading to significant morbidity and mortality. OSCC treatment is based on surgery and/or radiotherapy and/or chemotherapy. Immune Check point Inhibitors (ICIs) targeting PD-1 have been approved for recurrent and metastasic OSCC. However, only 15-20% of these patients are treated thanks to this anti-PD-1. Thus, there is a real need to improve the efficacy of ICIs in the treatment of HNSCC. The scRNAseq is a method which allows to study the tumoral heterogeneity, the microenvironment and the dynamic and regulation mecanisms in cells cancer. This technology could improve patient stratification, identify pronostic biomarkers, constitute an important tool in the therapeutical take care and lead to understand tumoral evolution and develop new prevention strategies. The project is organized into three cohorts: * Cohort A (OSCC): Designed to compare malignant cells directly with their healthy and pre-malignant counterparts within the same patient. * Cohort B (OPMD): Focused on patients with potentially malignant lesions but no active cancer. * Cohort C (Cyto-OPMD): Validating a non-invasive sampling method. The goal is to determine if a cytobrush can provide the same high-quality genomic data as a biopsy. By combining these approaches, the project aims to characterize the heterogeneity of all cell populations (tumour cells, stromal and immune microenvironment) to improve the global management of patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
150
* 1 or 2 tumoral specimen (depending on the size of the tumor). * 1 specimen of the healthy oral mucosa. * 1 OPMD specimen if applicable. The biospecimens will be collected at the time of the surgery organised for the standard routine medical care.
Blood sampling (6 mL), taken from a routine biological exam.
* 1 OPMD lesion specimen. * 1 specimen of the healthy oral mucosa (facultative). The biospecimens will be collected during standard routine medical care.
Centre Léon Bérard
Lyon, France
Characterization of the heterogeneity of all cell populations (tumor cells, stromal and immune microenvironment) in OSCC and OPMD using scRNA-seq.
Evaluation of transcriptomic data from all cell populations to define gene expression profiles and specific signatures.
Time frame: 4 years
Description of the functional interactions among tumor, stromal, and immune subpopulations.
Describe the functional interactions between tumor, stromal, and immune subpopulations identified by scRNA-seq and bulk RNA-seq using in vitro models and co-culture assays. Cellular responses will be assessed using transcriptomic analysis and phenotypic characterization.
Time frame: 4 years
Correlation between refined patient stratification (based on tumor, stromal and immune sub-population) and the impact on the response to ex-vivo treatments.
Correlation between tumor, stromal and immune sub-populations likely to refine patient stratification and the impact on the response to ex-vivo treatments.
Time frame: 4 years
Identification of prognostic and predictive biomarkers for oral squamous cell carcinoma evolution.
Correlation of gene expression profiles with disease progression to identify prognostic and predictive biomarkers in scRNAseq and bulk RNAseq datasets.
Time frame: 4 years
Evaluation of cytobrushing as a non-invasive sampling method for diagnostic yield equivalence to tissue biopsy in OPMD patients.
Comparative assessment of cytobrushing and tissue biopsy to establish diagnostic equivalence and evaluate the reduction of clinical constraints in the sampling of OPMD lesions.
Time frame: 4 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
* 1 cytobrush sample. * 1 OPMD lesion specimen. Samples must be collected in sequence (first the cytobrush, then the biopsy collected during standard routine medical care.).