TY - JOUR AU - Matias Autio, AU - Suvi-Katri Leivonen, AU - Oscar Brück, AU - Satu Mustjoki, AU - Judit Mészáros Jørgensen, AU - Marja-Liisa Karjalainen-Lindsberg, AU - Klaus Beiske, AU - Harald Holte, AU - Teijo Pellinen, AU - Sirpa Leppä, PY - 2021/03/01 Y2 - 2024/03/29 TI - Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma JF - Haematologica JA - haematol VL - 106 IS - 3 SE - Articles DO - 10.3324/haematol.2019.243626 UR - https://haematologica.org/article/view/9668 SP - 718-729 AB - 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. ER -