Characterisation of the Immune Infiltrate and Molecular Features of Thymic Epithelial Tumors Tumors (TETs)

Study Overview
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Brief Summary
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The IMMUNO-TET trial aims to assess the feasibility of characterising the immune environment of TETs and the constitutional and somatic molecular profiles of patients with localised thymic epithelial tumour (TET).

Detailed Description
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In this prospective study, patients undergoing thymectomy and thymomectomy as part of routine care undergo the following care pathway: During the pre-surgical visit (for n = 50 patients): as part of routine care, a blood sample is collected for analysis of CBC, leukocytes, lymphocytes, CRP, ferritinemia, TSH, T3L, T4L, anti-acetycholine receptor antibodies, …CMV, EBV, HSV, HIV serologies, …and HLA class I and class II typing. During thymectomy and thymomectomy surgery, the following samples are taken (for n = 50 patients): 6 blood samples on EDTA tubes are collected at the time of surgery for analyses. 3 fresh samples of the surgical specimen are taken by the pathologist: tumour T, juxta-tumour J and distant D locations for analyses by flow cytometry and RNA sequencing. Anatomopathology blocks/slides are also cut in the same way (tumour T, juxta-tumour J and distant D locations) for additional exploratory analyses. The feasibility of developing patient-derived xenografts (PDX) from TETs will be tested for n = 20 tumor samples. These models will allow to test potential therapeutic agents for this pathology. During the 1st month (+/- 7 days) post-surgery check-up, a blood sample is taken again (for n = 50 patients) for routine care: CBC, leukocytes, lymphocytes, CRP, ferritinemia, anti-acetycholine receptor antibodies and for peripheral immune system analysis at a distance from surgery and for constitutional molecular analysis. Informed consent is given to participate in this prospective study.

Official Title
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Characterisation of the Immune Infiltrate and Molecular Features of Thymic Epithelial Tumors Tumors (TETs)

Conditions
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Cancer

Intervention / Treatment
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* Other: single arm for all patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with suspicion of localised thymic epithelial tumour. Age ≥ 18 years. Treatment-naïve patient for this disease. Patient with an indication for thymectomy and thymomectomy in one of the partner centers. Signed informed consent form of the patient. Exclusion Criteria: Neoadjuvant chemotherapy. No social security affiliation. Person under legal protection. Other neoplasia in progress or cured within the last 3 years (except for operated carcinoma in situ).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm for all patients<br>single arm for all patients tumor samples will be taken for RNA sequencing of epithelial tumour cells during surgery. blood samples will be taken for Exome Sequencing (WES) at baseline, during surgery and one month post surgery. | Other: single arm for all patients<br>* tumor samples will be taken for RNA sequencing of epithelial tumour cells during surgery. blood samples will be taken for Exome Sequencing (WES) at baseline, during surgery and one month post surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| somatic molecular characterisation of TETs | description of genetic abnormalities in thymic tumours compared to non-tumourous thymic tissue (Whole Exome Sequencing RNA-sequencing technique, DNA Optical mapping); | 38 months | 
| Characterisation of the immune environment of TETs | description of immune cells in the tumour environment, description of tumour infiltrating T cells | 38 months | 
| Establishment of a patient-derived xenograft mouse model. |  | 38 months | 
| somatic molecular characterisation of TETs | Molecular constitutional characterisation of TETs with the technique of theExome Sequencing (WES) on blood samples of patients with TETs | 38 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genomic characterisation of TETs | WES data analysis constitutional genetic alterations will be performed. | 38 months | 
| Characterisation of potential alterations in signalling pathways to identify potential therapeutic targets | Molecular analyses will be performed to identify potential alterations in signalling pathways that can be targeted by new therapies. | 38 months | 
| Identification of potential neoepitopes | Analysis of TETs single-cell RNA-seq data will be performed. | 38 months | 
| Transcriptomic characterisation of TETs | Transcriptome sequencing analysis will be performed. | 38 months | 
| Epigenetic characterisation of TETs | Epigenetic characterisation of TETs will be performed by molecular analyses. | 38 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thymic epithelial tumors