Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
Suvi-Katri Leivonen,
Terhi Friman,
Matias Autio,
Samuli Vaittinen,
Andreas Wind Jensen,
Francesco d’Amore,
Stephen Jacques Hamilton-Dutoit,
Harald Holte,
Klaus Beiske,
Panu E. Kovanen,
Riikka Räty,
Sirpa Leppä
Affiliations
Suvi-Katri Leivonen
Applied Tumor Genomics Research Program, Medical Faculty, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki
Terhi Friman
Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
Matias Autio
Applied Tumor Genomics Research Program, Medical Faculty, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki
Samuli Vaittinen
Department of Pathology, Turku University Hospital, University of Turku, Turku
Andreas Wind Jensen
Department of Hematology, Aarhus University Hospital, Aarhus
Francesco d’Amore
Department of Hematology, Aarhus University Hospital, Aarhus
Stephen Jacques Hamilton-Dutoit
Institute of Pathology, Aarhus University Hospital, Aarhus
Harald Holte
Department of Oncology, Oslo University Hospital, Oslo, Norway
Klaus Beiske
Department of Pathology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
Panu E. Kovanen
Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University Hospital, Helsinki
Riikka Räty
Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
Sirpa Leppä
Applied Tumor Genomics Research Program, Medical Faculty, University of Helsinki, Helsinki, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki
Post-transplant lymphoproliferative disorders (PTLD) are iatrogenic immune deficiency-associated lymphoid/plasmacytic proliferations developing due to immunosuppression in solid organ or hematopoietic stem cell allograft patients. PTLD 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 (PTABCL). Epstein-Barr virus (EBV)-positive PT-ABCL 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) (hazard ratio =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 noninflamed 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, inflamed TME remained as an independent predictor for favorable outcome. We also compared TME between post-transplant and immunocompetent host diffuse large B-cell lymphomas (n=75) and discovered that the proportions of T cells were lower in PT-diffuse large B-cell lymphomas. In conclusion, we provide a comprehensive phenotypic characterization of PT-ABCL, highlighting the importance of immune cell composition of TME in determining the clinical behavior and prognosis of PT-ABCL.
