Nsclc
Conditions
Brief summary
Prospective, biological, observational study involving the collection and use of samples from patients suffering from NSCLC lung cancer, aimed at comparing the molecular profile related to metabolism among subjects with response or resistance to checkpoint inhibitors immune system (ICI), in order to contribute to define response biomarkers and new molecular pathways as therapeutic targets combine with ICI to overcome resistance.
Detailed description
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.
Interventions
None listed
Sponsors
Regina Elena Cancer Institute
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Study design
Observational model
FAMILY_BASED
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival OS | 24 months | The application of spatial transcriptomic approaches will enable the discovery of specific cellular niches that may be responsible for mechanisms of sensitivity or resistance to ICI. With the results you get, you will probably have a chance to locate it new and wonderful metabolic pathways capable of exerting their anti-tumor effect even in combination with ICIs. |
Countries
Italy
Contacts
CONTACTLorenza Landi, Doctor
PRINCIPAL_INVESTIGATORLorenza Landi, Doctor
IRCCS National Cancer Institute
Outcome results
None listed