Ricerc@Sapienza

Background:Immunotherapy has revolutionized treatments, prognosis and clinical outcome of several cancers. Anti-PD-1 agents represent the standard treatment in several tumors. However, despite the medium and long-term benefits achieved, a large proportion of patients is primary or secondary resistant to immunotherapy. One of the main mechanisms of resistance is the presence and subsequent establishment of an immunosuppressive microenvironment. Also, in Head and Neck cancer (HNSCC) paradigmatic example of a immunosuppressive tumor, immunotherapy is proposed after standard treatment however with limited efficacy.
Hypothesis:Our proposal stems from a strong evidence that CDK4/6 inhibitors (CDK4/6i) can significantly impact the immune-suppressive repertoire as off-target effect and this is associated with response to therapy in metastatic breast cancers. Thus, this immunological effect could be the key for subverting an immune-suppressive microenvironment, regardless its histology.
Aims:We propose a pilot study in which we will evaluate, in the HNSCC patients, the impact of one-month (window) treatment with CDK4/6i at standard dose in modulating TME architecture and components as well as circulating biomarkers of immunosuppression. Longitudinal patients¿samples, blood and biopsies/surgery, will be studied and characterized by participating research units to monitor and study changes in the TME, transcriptomic analysis and characterization of intratumor microbiome, Tregs and MDSCs in TME/peripheral blood and the association with clinical outcomes (ORR, OS and PFS)
Methodologies: The methodologies that will be employed include: Clinical trial management, Immune characterization of patient tumor samples (in-situ flex technology, RNAseq data and targeted sequencing of 16S and ITS ribosomal RNA) and blood (flow cytometry, multiplex, ELISA, HPLC-MS/MS method). Statistical elaboration of all data.