Immune Response Under Immunotherapy in Metastatic NSCLC: Sputum, Blood Samples and Microbioata Study

Study Overview
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Brief Summary
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Prospective pathophysiological exploratory monocentric study, focusing on adult patients with non-small cell lung cancer (NSCLC) : non-squamous type without oncogenic addiction, metastatic, treated with immune checkpoint inhibitors alone or in combination with chemotherapy in front line at the CHRU de Tours, France.

Detailed Description
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The percentage of patients benefiting from immunotherapy is quite low and their systemic side effects can sometimes be severe. One of the main difficulties is to identify before treatment patients who will respond to immune checkpoint inhibitors. Currently, the selection is done in a very large majority of cases on the expression of PD-L1 by the tumor. But this biomarker is not sufficient to identify patients responding or not to immune checkpoint inhibitors. In addition, factors extrinsic to the tumor, to its microenvironment and patient immunity may be involved in the response to immunotherapy such as the microbiota. The investigators therefore assume that the immune response in place during immunotherapy treatment differs according to the profile of patient response to immunotherapy. The main objective of this project is to describe local and systemic anti-tumor immune system of patients responders or not to immune checkpoint inhibitors, but also whether the immunological characterization of sputum could be a reflection of the microenvironment tumor. The secondary objective is to study the intestinal microbiota tract of patients receiving immunotherapy, depending on their consumption of antibiotics, and compare it to the pulmonary microbiota.

Official Title
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Immune Response Under Immunotherapy in Metastatic Non-Small Cell Lung Cancer: Sputum, Blood Samples and Microbiota Study

Conditions
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Non-squamous Lung Cancer, Metastatic Lung Cancer

Intervention / Treatment
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* Other: Blood
* Other: sputum
* Other: saliva
* Other: stool


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 18 years or over Diagnosis of metastatic NSCLC (Stage IV) adenocarcinoma only Absence of oncogenic addiction (EGFR, ALK, ROS1, RET, MET, BRAF) Treatment with ICI anti-PD1 or anti-PDL1 (pembrolizumab or atezolizumab) as 1st line treatment alone or in combination with chemotherapy and/or anti-angiogenic (bevacizumab). 1st injection of ICI, whether or not combined with chemotherapy Exclusion Criteria: Patient under judicial protection Pregnant or breastfeeding women NSCLC of the epidermal or undifferentiated type Opposition to data processing

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group<br>adult patients with adenocarcinoma type non-small cell lung cancer | Other: Blood<br>* Blood samples are taken at each visit to the day hospital for a programmed injection of immunotherapy.<br>Other: sputum<br>* induced by saline aerosol sputum during each visit to the day hospital for a programmed injection of immunotherapy.<br>Other: saliva<br>* spontaneous saliva during each visit to the day hospital for a programmed injection of immunotherapy.<br>Other: stool<br>* Stool analyses will be carried out on a sample taken by the patient at home and brought back at the time of a day hospital.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune and inflammatory response in the blood | T cell sub populations assessed by their relative abundance, and will be expressed as a percentage of total T cells B lymphocytes Cytokine inflammatory profile: the level of activation/regulation, production of cytokines and cytotoxicity markers will be analysed as a percentage of cells expressing the markers or producing the cytokines in relation to the total cell population (e.g. HLA-DR+, CD38+, Bcl-2lo phenotype of CD8 T lymphocytes) | 30 months | 
| Immune and inflammatory response in the airways | T cell sub populations assessed by their relative abundance, and will be expressed as a percentage of total T cells B lymphocytes Cytokine inflammatory profile: the level of activation/regulation, production of cytokines and cytotoxicity markers will be analysed as a percentage of cells expressing the markers or producing the cytokines in relation to the total cell population (e.g. HLA-DR+, CD38+, Bcl-2lo phenotype of CD8 T lymphocytes) | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of gut microbiota | characterisation of gut microbiota (16S rRNA sequencing) | 30 months | 
| Analysis of lung microbiota | characterisation of lung microbiota (16S rRNA sequencing) | 30 months | 
| perform blood pembrolizumab assays. | antibodies dosage | 30 months | 
| perform sputum pembrolizumab assays. | antibodies dosage | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood sample, sputum, microbiota, Immunotherapy, saliva