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

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 an...

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Autores principales: Leivonen, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620595/
https://www.ncbi.nlm.nih.gov/pubmed/37259566
http://dx.doi.org/10.3324/haematol.2023.282831
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author Leivonen, 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
author_facet Leivonen, 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
author_sort Leivonen, Suvi-Katri
collection PubMed
description 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 (PT-ABCL). 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.
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spelling pubmed-106205952023-11-03 Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas Leivonen, 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 Haematologica Article - Non-Hodgkin Lymphoma 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 (PT-ABCL). 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. Fondazione Ferrata Storti 2023-06-01 /pmc/articles/PMC10620595/ /pubmed/37259566 http://dx.doi.org/10.3324/haematol.2023.282831 Text en Copyright© 2023 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article - Non-Hodgkin Lymphoma
Leivonen, 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
Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
title Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
title_full Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
title_fullStr Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
title_full_unstemmed Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
title_short Characterization and clinical impact of the tumor microenvironment in post-transplant aggressive B-cell lymphomas
title_sort characterization and clinical impact of the tumor microenvironment in post-transplant aggressive b-cell lymphomas
topic Article - Non-Hodgkin Lymphoma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620595/
https://www.ncbi.nlm.nih.gov/pubmed/37259566
http://dx.doi.org/10.3324/haematol.2023.282831
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