Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Immunomodulating Agents

Tumor samples will be collected by the pathologist at the reception of the tumor removed during surgery

Tumor samples

Charlotte DOMBLIDES

Matthieu THUMEREL

Immunotherapy have revolutionized the field of oncology, but response rates are low and all patients relapse, due to cellular and soluble immunosuppressive mechanisms. These immunosuppressive mechanisms will be better characterized and their involvement in therapeutic responses in non-small cell lung cancers (NSCLC). Indeed, large transcriptomic analysis of different subsets of immunosuppressive cells will performed, correlating them to clinical outcome in a cohort of stage III disease, treated by radiochemotherapy and immunotherapy as maintenance, and stage IV treated by immunotherapy as first-line treatment. Furthermore, we will analyse cellular mechanisms by in vitro studies, assessing the effect of immunosuppressive cells, provided by fresh tumor samples, on phenotype and functions of lung cancer cell lines. The aim of this study is to better characterize immunosuppressive landscape of NSCLC and mechanisms involved in their protumor functions.

In recent years, immune-based therapies have revolutionized the field of oncology by significantly improving survival of cancer patients. Despite sustained responses, only 20% to 40% of cancer patients respond. It has become clear that the immunosuppressive environment induced by tumor through cellular and/or soluble pathways critically contribute to hinder efficient antitumor immunity. The inhibition of these immunosuppressive networks thus represents an essential prerequisite for the improvement of responses to anticancer immunotherapies. Several immune and non -immune cell populations have been identified as key actors of tumor-induced immunosuppression, among which are myeloid-derived suppressor cells (MDSC), and cancer associated fibroblasts (CAF). However, in non-small cell lung cancers (NSCLC), the phenotypic characteristics and the prognostic role of these cells, the mechanisms underlying their immunosuppressive functions, and their role in dampening the efficacy of immunotherapies in clinical practice are less characterized. The aim of this project is to better characterize these different immunosuppressive subpopulations, and to study their role promoting NSCLC development and resistance to immunotherapies.

First the tumor CAF and immunosuppressive microenvironment using single cell RNA sequencing will be characterized (objective 1a). After identification of phenotypic markers, the immunosuppressive landscape of stage III NSCLC on a lung cancer cohort treated at Bordeaux University Hospital will be analysed, and data on CAF, MDSC and immune infiltration will be correlated with tumor characteristics and cancer outcome (objective 1b). Finally, the pro-tumor functions of CAF isolated from lung cancer patients will be assessed in vitro (objective 2).

Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies

Exploratory analysis of the immune infiltration (phenotype and function of immunosuppressive and antitumor immune cells) and of the cancer-associated fibroblasts through a transcriptomic analysis of fresh resected lung carcinoma, comparing patients with lymph node involvement or not. Bioinformatics analysis of gene panels

Analyze CAF and immunosuppressive immune infiltration in a cohort of unresectable stage III lung carcinoma treated with radiochemotherapy followed by immunotherapy, assessing correlation between immunosuppressive subpopulations and clinical parameters and patient outcome. We will use a multiplexing immunofluorescence assay

Functional in vitro studies of the effect of CAF on phenotype and function of T lymphocytes and of MDSC being extracted from resected NSCLC prospectively collected

University Hospital, Bordeaux

Rare Diseases

Oculocerebral Syndrome With Hypopigmentation

Immunotherapy have revolutionized the field of oncology, but response rates are low and all patients relapse, due to cellular and soluble immunosuppressive mechanisms. MDSC are one of the most important immunosuppressive cells, that also harbour non immunologic functions, favouring cancer invasion. These non immunologic functions of MDSC in lung cancer will be better characterized. Indeed, cellular mechanisms will be analysed by in vitro studies, assessing the effect of immunosuppressive cells, provided by fresh tumor samples, on phenotype and functions of lung cancer cell lines. The aim of this study is to better characterize immunosuppressive landscape of NSCLC and mechanisms involved in their protumor functions.

In recent years, immune-based therapies have revolutionized the field of oncology by significantly improving survival of cancer patients. Despite sustained responses, only 20% to 40% of cancer patients respond. It has become clear that the immunosuppressive environment induced by tumor through cellular and/or soluble pathways critically contribute to hinder efficient antitumor immunity. The inhibition of these immunosuppressive networks thus represents an essential prerequisite for the improvement of responses to anticancer immunotherapies. Several immune cell populations have been identified as key actors of tumor-induced immunosuppression, among which are myeloid-derived suppressor cells (MDSC) and regulatory T lymphocytes (Treg). However, in non-small cell lung cancers (NSCLC), the prognostic role of these cells, the mechanisms underlying their immunosuppressive functions, their "non-immunological" protumoral functions and their role in dampening the efficacy of immunotherapies in clinical practice are less characterized. The aim of this project is to better characterize the non immunologic functions of MDSC. We propose to assess in vitro the non-immunological pro-tumor functions of MDSC isolated from lung cancer patients

Role of MDSCs and Cancer Stem Cells and Their Cross Talks in NSCLC

Role of Myeloid Derived Suppressive Cells (MDSCs) and Cancer Stem Cells and Their Cross Talks in Non-Small Cell Lung Cancer (NSCLC)

Functional in vitro studies of the effect of MDSC extracted from resected NSCLC prospectively collected on phenotype and function of lung cancer cell lines

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Hematinics

Liver Extracts

for each patient: liver sampling, blood samples ( serum, plasma, PBMC, whole blood), per-endoscopic bile sampling, stool samples, and materials derived from fresh tumors

Christophe Tournigand, MD-PHD

Ilaria Cascone, PHD

Pr Tournigand

Colorectal and pancreatobiliary cancers are the most common digestive cancers. Their incidence has particularly increased over the last few decades, leading to suspicion that environmental factors are involved. In addition, strategies for the therapeutic management of these cancers are evolving in the context of the development of immunotherapies.

Tumor microenvironment is a potential source of new diagnostic, prognostic and predictive markers and new therapeutic targets. The links between tumor microenvironment and modulation of the immune system in colorectal and pancreatobiliary cancers are poorly understood. Molecular classifications have been proposed for these cancers, but their link with immunity and response to treatment remains to be explored.

Objective : explore links between molecular subtypes, tumor microenvironment, host (immune system, pre-metastatic niche, intestinal microbiota, metabolism), and survival (prognostic value), response (predictive value) and tolerance (toxicities) to treatments in digestive cancers, in particular colorectal and pancreatobiliary cancers.

Method: Retrospective and prospective monocentric cohort study

Retrospective and prospective monocentric cohort study

Microenvironment and Immunity of Digestive Cancers - East Paris Multicentric Cohort

Interactions Between Tumor, Tumor Microenvironment and Immune System in Digestive Cancers : Impact on Survival and Response to Treatment

AP-HP is the owner of the data and no use or transmission to a third party may be made without its prior consent.

Overall survival (OS): vital status (alive/deceased)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies	NCT06024538	Lung Neoplasm Cancer Associat... Myeloid-Derived...	Tumor samples	18 Years -	University Hospital, Bordeaux
Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies	NCT06024538	Lung Neoplasm Cancer Associat... Myeloid-Derived...	Tumor samples	18 Years -	University Hospital, Bordeaux
Role of MDSCs and Cancer Stem Cells and Their Cross Talks in NSCLC	NCT06024226	Lung Neoplasms Myeloid-Derived... Immunosuppressi...	Tumor samples	18 Years -	University Hospital, Bordeaux
Microenvironment and Immunity of Digestive Cancers - East Paris Multicentric Cohort	NCT04707365	Colorectal Canc... Pancreas Tumor Biliary Tract T... Immune System a...	Tumor samples	18 Years -	Assistance Publique - Hôpitaux de Paris
Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies	NCT06024538	Lung Neoplasm Cancer Associat... Myeloid-Derived...	Tumor samples	18 Years -	University Hospital, Bordeaux

Spots Global Cancer Trial Database for tumor samples