Immunomonitoring in patients affected by metastatic clear cell renal carcinoma in treatment with Tyrosine-kinase inhibitors and immune check point inhibitors
| Componente | Categoria |
|---|---|
| Salvatore Caponnetto | Dottorando/Assegnista/Specializzando componente il gruppo di ricerca / PhD/Assegnista/Specializzando member of the research group |
| Hassan Rahimi Koshkaki | Componenti il gruppo di ricerca / Participants in the research project |
| Chiara Napoletano | Componenti il gruppo di ricerca / Participants in the research project |
| Aurelia Rughetti | Componenti il gruppo di ricerca / Participants in the research project |
| Sabino Carbotta | Componenti il gruppo di ricerca / Participants in the research project |
Immune check point inhibitors (ICI) are recently approved for the treatment of metastatic renal cell carcinomas (mRCC) after the first line of therapy with Tyrosine Kinase Inhibitors (TKI) (sunitinib and pazopanib) that specifically target TK involved in the regulation of numerous aspect of cell life. The introduction of these new drugs that act on immune system makes mandatory to define possible biomarkers of immune-fitness to improve the management of these drugs to enhance their efficacy and reduce their toxicity.
Objectives of this study are to evaluate the immune profile of mRCC patients before, during and after treatment with pazopanib or sunitinib and before and during treatment with Nivolumab and identify biomarkers/immune requirements of response and early immune signs of toxicity.
Immunological ex-vivo methodology will be applied using periodically peripheral blood withdrawals before, during and at the end of each therapy. Immune-fitness will be evaluated on all T cell sub-populations (markers of activation and inhibition, cytokine production, proliferation and suppression, exhaustion, immunoscore, gene profiling), on DC population differentiated from monocytes (marker of activation, endocytosis, gene profiling) and on serum markers (cytokines/chemokines relevant during anticancer immune response/tumor progression).
Immune algorithm will be designed and possibly related to clinical and toxicity outcome of patients.
Expected results:
1. Definition of biomarkers of response related to the activity of the drug on DCs and T cells (plasmatic release of microvesicles, biomarkers of response on activated T cells etc.)
2. Definition of biomarkers of toxicity early identifying immune-signals correlated with auto-immunity.
3. Definition of novel criteria for eligibility of cancer patients to immunotherapy protocols based on immune fitness and not on empirical parameters (not immune-related)