A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

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




TekijätLeivonen Suvi-Katri, Friman Terhi, Autio Matias, Vaittinen Samuli, Jensen Andreas Wind, d'Amore Francesco, Hamilton-Dutoit Stephen Jacques, Holte Harald, Beiske Klaus, Kovanen Panu E., Räty Riikka, Leppä Sirpa

Julkaisuvuosi2023

JournalHaematologica

Tietokannassa oleva lehden nimiHAEMATOLOGICA

Vuosikerta108

Numero11

Aloitussivu3044

Lopetussivu3057

ISSN0390-6078

eISSN1592-8721

DOIhttps://doi.org/10.3324/haematol.2023.282831

Verkko-osoitehttps://haematologica.org/article/view/haematol.2023.282831

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/381042205


Tiivistelmä

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.


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