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 Kovanen, Riikka Räty, Sirpa Leppä

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

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 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, 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.
Originalspråkengelska
TidskriftHaematologica
Volym108
Nummer11
Sidor (från-till)3044-3057
Antal sidor14
ISSN0390-6078
DOI
StatusPublicerad - 1 nov. 2023
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 3122 Cancersjukdomar

Citera det här