Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas.

Abstract

Post-transplant lymphoproliferative disorders (PTLDs) are iatrogenic immune deficiencyassociated lymphoid/plasmacytic proliferations developing due to immunosuppression in solid organ or hematopoietic stem cell allograft patients. PTLDs are characterized by abnormal proliferation of lymphoid cells and have a heterogeneous clinical behavior. We profiled expression of >700 tumor microenvironment (TME)-related genes in 75 post-transplant aggressive B-cell lymphomas (PT-ABCLs). EBV-positive PT-ABCLs clustered together and were enriched for type I interferon pathway and antiviral response genes. Additionally, a cytotoxicity gene signature associated with EBV-positivity and favorable overall survival (OS; HR 0.61, P=0.019). In silico immunophenotyping revealed two subgroups with distinct immune cell compositions. The inflamed subgroup with higher proportions of immune cells had better outcome compared to non-inflamed subgroup (median OS >200.0 vs. 15.2 months, P=0.006). In multivariable analysis with EBV status, International Prognostic Index, and rituximab-containing treatment, the inflamed TME remained as an independent predictor for favorable outcome. We also compared the TME between posttransplant and immunocompetent host diffuse large B-cell lymphomas (DLBCLs) (n=75) and discovered that the proportions of T cells were lower in PT-DLBCL. In conclusion, we provide a comprehensive phenotypic characterization of PT-ABCLs, highlighting the importance of immune cell composition of TME in determining the clinical behavior and prognosis of PT-ABCL.