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.
consecutive patients
lung carcinoma surgically treated by surgery only (objectives 1a and 2), or stage III lung carcinoma treated by concomitant radiochemotherapy followed by durvalumab (maintenance) treated between September 2018 and december 2021 (objective 1b)
patient receiving chemotherapy, radiotherapy or immunotherapy in the neoadjuvant setting (all objectives)
patient with previous cancer
Patients with lung carcinoma surgically treated by surgery only, or stage III lung carcinoma treated by concomitant radiochemotherapy followed by durvalumab (maintenance) treated between September 2018 and december 2021
Cohort
Prospective
Tumor samples
Procedure/SurgeryTumor samples will be collected by the pathologist at the reception of the tumor removed during surgery
Descriptive analysis of immune infiltration and phenotypic and functional characteristics of the different cell subgroups isolated from fresh tumors
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
Correlation between the infiltration of CAF and immunosuppressive immune cells and with clinicopathological parameters and patient prognosis (relapse free-survival, overall survival) in stage III NSCLC exposed to immunotherapy
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
Comparative analysis of the modifications of phenotype and functions of MDSC and T lymphocytes when exposed to CAF extracted from patient tumor tissue
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
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