Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma

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  • Matias Autio, University of Helsinki
  • ,
  • Suvi-Katri Leivonen, University of Helsinki
  • ,
  • Oscar Brück, University of Helsinki
  • ,
  • Satu Mustjoki, University of Helsinki
  • ,
  • Judit Mészáros Jørgensen
  • Marja-Liisa Karjalainen-Lindsberg, Helsinki University Hospital
  • ,
  • Klaus Beiske, University of Oslo
  • ,
  • Harald Holte, University of Oslo
  • ,
  • Teijo Pellinen, Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
  • ,
  • Sirpa Leppä, University of Helsinki

Tumor microenvironment (TME) and limited immune surveillance play important roles in lymphoma pathogenesis. Here, we aimed to characterize immunological profiles of diffuse large B-cell lymphoma (DLBCL), and predict the outcome in response to immunochemotherapy. We profiled the expression of 730 immune-related genes in tumor tissues of 81 patients with DLBCL utilizing the Nanostring platform, and used multiplex immunohistochemistry to characterize T-cell phenotypes, including cytotoxic T-cells (CD8, Granzyme B, OX40, Ki67), T-cell immune checkpoint (CD3, CD4, CD8, PD1, TIM3, LAG3), as well as regulatory T-cells and Th1 effector cells (CD3, CD4, FOXP3, TBET) in 188 patients. We observed a high degree of heterogeneity at the transcriptome level. Correlation matrix analysis identified gene expression signatures with highly correlating genes - the main cluster containing genes for cytolytic factors, immune checkpoint molecules, T-cells and macrophages, together entitled as a TME immune cell signature. Immunophenotyping of the distinct cell subsets revealed that a high proportion of immune checkpoint positive T-cells translated to unfavorable survival. Together, our results demonstrate that the immunological profile of DLBCL TME is heterogeneous and clinically meaningful. This highlights the potential impact of T-cell immune checkpoint in regulating survival and resistance to immunochemotherapy.

OriginalsprogEngelsk
TidsskriftHaematologica
Vol/bind106
Nummer3
Sider (fra-til)718-729
Antal sider12
ISSN0390-6078
DOI
StatusUdgivet - mar. 2021

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