Adaptive Immune Response and Systemic Inflammation Predict Survival in High-Grade B-Cell Lymphoma with MYC/BCL2/BCL6 Rearrangements

High-grade B-cell lymphomas with concurrent MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) represent an aggressive subgroup of B-cell malignancies with limited therapeutic options and poor survival outcomes. Despite growing recognition of the tumor microenvironment (TME) as a determinant of prognosis in hematologic cancers, its role in HGBL-DH/TH has not been systematically evaluated. Here, we characterize the adaptive immune landscape in 47 HGBL-DH/TH cases compared with 27 triple-negative diffuse large B-cell lymphomas (tnDLBCL) using next-generation sequencing of T-cell receptor (TCR) β-chain repertoires. Systemic inflammation was assessed using the Glasgow Prognostic Score (GPS), and TME features were further profiled immunophenotypically.

Our findings reveal that HGBL-DH/TH harbors a distinctive TCR repertoire, including clonotypes absent in tnDLBCL, indicative of selective tumor-driven immune responses. Measures of TCR clonality and dominant clone frequency correlated with overall survival, whereas GPS was predictive of both overall and progression-free survival. Multivariate analysis identified GPS and the revised International Prognostic Index (R-IPI) as the strongest independent prognostic indicators. These results suggest that a combination of systemic inflammatory status and the composition of tumor-directed T-cell responses defines outcome in HGBL-DH/TH, highlighting potential avenues for immune-based risk stratification and therapeutic intervention.