This project aims to identify and characterize soluble molecules secreted by malignant B lymphocytes that suppress the formation and function of the immunological synapse (IS) in T lymphocytes, in the context of B cell-derived hematologic malignancies, namely chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and non-Hodgkin lymphomas (NHL) with peripheral blood involvement. Through an integrated approach combining transcriptomic profiling (RNA sequencing), multiplex immunoassays (ELISA), flow cytometry, and advanced imaging techniques (confocal and super-resolution microscopy), we will define the immunosuppressive soluble factor signatures associated with each malignancy. The main goals are:
(i) to uncover disease-specific or shared soluble mediators that impair T cell activation and effector functions;
(ii) to validate their effects in primary patient samples;
(iii) to evaluate the potential of neutralizing antibodies in restoring T cell responses.
Expected outcomes include the identification of novel soluble targets involved in immune evasion, paving the way for innovative immunotherapeutic strategies aimed at reactivating T cell function in currently incurable B cell cancers.

Disclaimer: This project has been funded under Contract Num P2022PSMX4_001 Mission 4 Component 2 (M4C2) – 1.1: Fondo per il Programma Nazionale Ricerca (PNR) e progetti di Ricerca di Significativo Interesse Nazionale (PRIN) del Piano Nazionale di Ripresa e Resilienza (PNRR), European Union “Next Generation EU”, 2022.