Immune Metabolism Dysregulation and Efficacy to Anti-PD-1 PD-L1 Agents in Non Small Cell Lung Cancer Patients

This study aims to identify the metabolic pathways related to the tumor microenvironment in NSCLC patients and their role in the response to ICI.

To this end, the metabolic picture will be evaluated on tumor-associated fibroblasts and macrophages tumor-associated and tumor-infiltrating lymphocytes, obtained from tissue samples of two different cohorts of patients candidate to receive immune-checkpoint treatment inhibitors. Furthermore it will correlate metabolic alterations in tumor tissues and peripheral immune cells or in plasma proteins of NSCLC patients with clinical response to ICIs.

For this purpose, serum/plasma and peripheral blood mononuclear cells (PBMC) will be isolated from the peripheral blood of patients to carry out phenotypic, metabolic and transcriptional studies on cells peripheral immune system. Finally it will come explored the therapeutic modulation of metabolic signatures identified in ex vivo models, using organoids and cultures of organotypic tissue sections obtained from patients affected by NSCLC, subjected to curative surgical treatment and treatment naive.

Inclusion criteria

• Age > 18 years
• Histological diagnosis of advanced stage NSCLC
• Histotype adenocarcinoma and squamous carcinoma
• ECOG PS <2
• Known PDL-1 stage
• Measurable disease
• Availability of tumor tissue
• No evidence of molecular drivers
• Written informed consent (to the study and data processing)

For the second cohort in addition to the precedents it is included

• Diagnosis of limited or locally advanced NSCLC deemed resectable

For the third cohort in addition to the precedents it is included

• patients candidates for surgery for non-small cell lung cancer

Exclusion criteria

• Contraindications to immunotherapy
• Unavailability of tumor tissue
• Histotype with neuroendocrine or mixed component

For the second cohort

• Contraindication to immunotherapy
• Histotype with neuroendocrine or mixed component
• Locally advanced disease candidate for concomitant chemo-radiotherapy treatment

For the third cohort

• previously treated patients