Glioma, Non Hodgkin Lymphoma, Non Small Cell Lung Cancer
Conditions
Keywords
Non Hodgkin Lymphoma, glioma, lung cancer, HIV, transplantation, brain
Brief summary
The explosion of novel therapies targeting tumor mutations or immune molecules requests to define or better characterize the mutational profiles of tumors that are none or insufficiently explored so far. This is particularly the case for tumors arising in immune-suppressed individuals or environments which have been poorly, if any, analyzed so far with modern molecular methods. The goal of the translational research program, Ideation, is to define novel biomarkers such as the tumor mutational profiling and immunomutanome in such contexts and to compare the results obtained to those observed in immune competent individuals. In addition, this approach will allow to characterize novel key non-invasive diagnostic and prognostic biomarkers such as circulating tumoral DNA and cells. Altogether results will provide novel biomarkers to better adapt therapeutic strategies in these cancers, to monitor response to treatment as well as to define new molecular targets of potential therapeutic strategies.
Detailed description
The main objective is to discover novel invasive and non-invasive immuno-molecular actionable biomarkers in rare but severe tumors arising in immune-suppressed compared for some tumors in immune-competent patients. Indeed, this tumors present a deficient immune environment, either due to the host acquired immune deficiency, i.e. transplantations or HIV infection, or because the diseased tissue belongs in an immune sanctuary as the brain. The primary hypothesis, in this context, is that these tumor mutational profiles and their changes during drug therapy must be influenced by the immune environment and response. This must lead to differences from similar tumors observed in immune-competent environments (immunocompetent individuals or tissues expressing immunity), responsible for: modification in the molecular targets for appropriate drugs ; alteration of tumor immunogenicity and of future immune-based therapies ; specific biomarkers for monitoring the response to drug therapy. The objectives of this program are to carry on invasive and non-invasive investigations in order to define the mutational profile of these free types of severe tumors, non-Hodgkin lymphoma (NHL), lung cancers and gliomas arising in hosts or tissues with altered immunity. These investigations will lead to : identify novel invasive and non-invasive biomarkers for predicting and evaluating efficacy of future personalized and immune-based therapies; compare tumors from immune-suppressed and immune-competent hosts; discover hot spots of tumoral mutations as mechanisms of tumors resistance, new molecular targets for future molecular and immune-bases therapeutic strategies; define the tumor immunomutanome as a score of neo-epitopes predicting: tumor immunogenicity, disease outcome and efficacy of immunotherapies; detect non-invasive tumoral biomarkers from liquid biopsies based on Circulating tumoral DNA and Circulating tumoral Cells to facilitate future diagnosis and monitoring of such tumors; identify biomarkers of tumor escape or resistance to treatments.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Followed at Pitié-Salpêtrière hospital, Tenon hospital, Henri Mondor hospital, Saint-Louis hospital or intercommunal hospital center of Créteil * Histological diagnosis confirmed of: * Non-small cell lung cancer (adenocarcinoma, squamous cell, large cells) related to HIV, or * Immunocompetent non-small cell lung cancer (adenocarcinoma, squamous cell, large cells), or * Non-Hodgkin's lymphoma (NHL): HIV-related NHL, post-transplant lymphoproliferation (LPT) according to WHO (World Health Organization) 2016 classification, primary CNS (central nervous system) lymphoma (LPS), or * Primary CNS lymphoma * Immunocompetent NHL: diffuse large B cell lymphoma (ABC or GC) * Glioma * Naïve cancer treatment (except for the specific case of gliomas with certain or possible activation of MAPK (Mitogen-activated protein kinases) and MMR (Mismatch Repair) inactivation). * Cancer undergoing surgery for excision or a large biopsy (pleural biopsy under video-thoracoscopy, mediastinoscopy, biopsy lymph node excision or cutaneous or cerebral metastasis). * For patients with NSCLC: hemoglobin level\> 9 g / dL; for patients with NHL or glioma: hemoglobin \> 7 g / dL. * Weight ≥ 48 kg. * Informed consent to participation signed before carrying out any specific procedure of the study. * Affiliation to the French social security system.
Exclusion criteria
* Other cancer than those in the study: * For NHL after transplantation: marginal zone NHL, follicular NHL, mantle cell NHL, lymphoplasmocytic NHL (non-WHO lymphoma as LPT) * For HIV-related LPTs and NHLs: LPS * For LPT: tumor EBV status unknown * For immunocompetent NHL: other NHL than diffuse large B cell lymphoma * For lung cancers: small cell lung cancer * Absence of tumor material, blood or saliva samples taken before the start of chemotherapy (except for the specific case of gliomas with certain or possible activation of MAPK and MMR inactivation) * Major under guardianship or curatorship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prognostic value of the tumor invasive biomarkers | at Day 0 | Analyze of the tumor biomarkers on frozen biopsy for the three types of cancer (NHL, lung cancer and glioma) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of tumoral biomarkers | at Day 0 | i) the mutational tumor profile by using a next generation sequencing (NGS) comparingson of the tumor DNAgenome with the patient's constitutional genome (sequenced on blood or saliva) for the three types of cancer (NHL, lung cancer and glioma) and ii) immunomutanome and score of neo-epitopes defined by tumor RNA-sequencing defining the specific mutants expressed in the tumor and able to be recognized by the immune system. |
| Prognostic value of the tumor non invasive biomarkers | at Day 0, Month 3 and Month 6 | The analysis of circulating DNA (ctDNA) will be performed from plasma collected from the prospective cohort of the patients for the three types of cancer (NHL, lung cancer and glioma). DNA will be extracted and amplified followed by Next-Generation Sequencing (NGS) and Droplet digital PCR (ddPCR) analysis for the identification of new biomarkers and/or for the follow up of mutations previously identified on tumor DNA. Results will be compared to tissue results in each group and to CTCs results in the Lung cancer group and prognostic values of these biomarkers will be assessed from clinical datas. |
| Prognostic value of the tumor non-invasive biomarkers | at Day 0, Month 3 and Month 6 | The analysis of circulating tumor cells (CTCs) will be performed from whole peripheral blood collected from the prospective cohort of patients with lung cancer infected or not with HIV. CTC fraction will be prepared from a cell size-based enrichment protocol. Then, DNA and RNA will be extracted and amplified followed by Next-Generation Sequencing (NGS) and RNA sequencing for the identification of new biomarkers. Droplet digital PCR (ddPCR) analysis will also be performed for validation and patient follow-up. Mutations and expression data in CTC will be compared to tissue and ctDNA in the two groups and prognostic values of these biomarkers will be assessed from clinical datas. |
Countries
France
Outcome results
None listed