Research projects

D

iffuse large B-cell lymphoma (DLBCL) is the most common malignant lymphoid neoplasm in adults and represents a heterogeneous group of tumors with distinct subtypes that differ in genetic alterations, clinical outcomes, treatment responses, and prognosis. Approximately 5-15% of DLBCL cases are high-grade B-cell lymphomas with MYC and BCL2 rearrangements, known as double-hit lymphomas (HGBCL-DH-BCL2). Due to the simultaneous activation of these key oncogenes, HGBCL-DH-BCL2 is among the most aggressive and chemotherapy-resistant lymphoma subtypes, with limited treatment options and a poor prognosis.

Based on transcriptomic analyses conducted in our lab, these aggressive lymphomas show increased unfolded protein response (UPR) activity, along with reduced expression of immune and inflammatory signatures, suggesting a decreased reliance on the microenvironment.

Studying the unique biology of these tumors in relation to UPR, the inflammatory microenvironment, and antigen presentation regulation, using patient samples and preclinical disease models, could provide a rational foundation for exploring targeted agents in combination with immunotherapies that enhance tumor recognition and elimination.

Our study aims to provide a better understanding of the dysregulated UPR signaling in this lymphoma type, as well as potential new strategies for treating these aggressive B-cell lymphomas that have a very unfavorable prognosis with standard therapies.