Browsing by Subject "CLASS-II EXPRESSION"

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  • Pollari, Marjukka; Pellinen, Teijo; Karjalainen-Lindsberg, Marja-Liisa; Kellokumpu-Lehtinen, Pirkko-Liisa; Leivonen, Suvi-Katri; Leppä, Sirpa (2020)
    Objectives Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive extranodal lymphoma. We have previously shown that high content of tumor-infiltrating lymphocytes (TILs) and PD-1 expressing TILs associate with better survival in T-DLBCL. In this study, we have further characterized distinct TIL subtypes and their proportions in association with patient demographics and survival. Methods We used multiplex immunohistochemistry to characterize TIL phenotypes, including cytotoxic T-cells (CTLs; CD8(+), OX40(+), Granzyme B+, Ki-67(+), LAG-3(+), TIM-3(+), PD-1(+)), CD4(+)T-cells (CD3(+), CD4(+), TIM-3(+), LAG-3(+)), regulatory T-cells (Tregs; CD3(+), CD4(+), FoxP3(+)), and T helper 1 cells (Th1; CD3(+), CD4(+), T-bet(+)) in 79 T-DLBCLs, and correlated the findings with patient demographics and outcome. Results We observed a substantial variation in TIL phenotypes between the patients. The most prominent CD8(+)TILs were Ki-67(+)and TIM-3(+)CTLs, whereas the most prominent CD4(+)TILs were FoxP3(+)Tregs. Despite the overall favorable prognostic impact of high TIL content, we found a subpopulation of T-bet(+)FoxP3(+)Tregs that had a significant adverse impact on survival. Lower content of CTLs with activated or exhausted phenotypes correlated with aggressive clinical features. Conclusions Our results demonstrate significant variation in TIL phenotypes and emphasize the adverse prognostic impact of Tregs in T-DLBCL.
  • Dufva, Olli; Pölönen, Petri; Brück, Oscar; Keränen, Mikko A. I.; Klievink, Jay; Mehtonen, Juha; Huuhtanen, Jani; Kumar, Ashwini; Malani, Disha; Siitonen, Sanna; Kankainen, Matti; Ghimire, Bishwa; Lahtela, Jenni; Mattila, Pirkko; Vähä-Koskela, Markus; Wennerberg, Krister; Granberg, Kirsi; Leivonen, Suvi-Katri; Meriranta, Leo; Heckman, Caroline; Leppä, Sirpa; Nykter, Matti; Lohi, Olli; Heinäniemi, Merja; Mustjoki, Satu (2020)
    Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-γ response in lymphoma. CIITA methylation regulating antigen presentation, cancer type-specific immune checkpoints, such as VISTA in myeloid malignancies, and variation in cancer antigen expression further contributed to immune heterogeneity and predicted survival. Our study provides a resource linking immunology with cancer subtypes and genomics in hematological malignancies.
  • Leivonen, Suvi-Katri; Pollari, Marjukka; Brück, Oscar; Pellinen, Teijo; Autio, Matias; Karjalainen-Lindsberg, Marja-Liisa; Mannisto, Susanna; Kellokumpu-Lehtinen, Pirkko-Liisa; Kallioniemi, Olli; Mustjoki, Satu; Leppä, Sirpa (2019)
    Primary testicular lymphoma is a rare lymphoid malignancy, most often, histologically, representing diffuse large B-cell lymphoma. The tumor rnicroenvi.ro.nrnent and limited immune surveillance have a major impact on diffuse large B-cell lymphoma pathogenesis and. survival, but the impact on primary testicular lymphoma is unknown. Here, the purpose of the study was to characterize the tumor microenvironme.nt in primary testicular lymphoma, and associate the findings with outcome. We profiled the expression of 730 immune response enes in 60 primary testicular lymphomas utilizing the Nanostring platorm, and used multiplex imrnunohistochemistry to characterize the immune cell phenotypes in the tumor tissue. We identified a gene signature enriched for T-lymphocyte markers differentially expressed. between the patients. Low expression of the signature predicted poor outcome independently of the International Prognostic Index (progression -free survival: HR=2.810, 95%CI: 1.228-6.431, P=0.014; overall survival: HR=3.267, 95`)/0' CI: 1.406-7.590, P=0.006). The T-lymphocyte signature was associated with outcome also in an independent diffuse large B-cell lymphoma cohort (n=96). Multiplex immunohistochemistry revealed that poor survival of primary testicular lymphoma patients correlated with low percentage of CD3'CD4' and CD3+CD8' tumor-infiltrating lymphocytes (P
  • Pollari, Marjukka; Leivonen, Suvi-Katri; Leppä, Sirpa (2021)
    Simple Summary Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive lymphoma entity that mainly affects elderly men. It has a high relapse rate with especially the relapses of the central nervous system associating with dismal outcome. T-DLBCL has a unique biology with distinct genetic characteristics and clinical presentation, and the increasing knowledge on the tumor microenvironment of T-DLBCL highlights the significance of the host immunity and immune escape in this rare lymphoma, presenting in an immune-privileged site of the testis. This review provides an update on the latest progress made in T-DLBCL research and summarizes the clinical perspectives in T-DLBCL. Primary testicular lymphoma is a rare lymphoma entity, yet it is the most common testicular malignancy among elderly men. The majority of the cases represent non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) with aggressive clinical behavior and a relatively high relapse rate. Due to the rareness of the disease, no randomized clinical trials have been conducted and the currently recognized standard of care is based on retrospective analyses and few phase II trials. During recent years, the tumor microenvironment (TME) and tumor-related immunity have been the focus of many tumor biology studies, and the emergence of targeted therapies and checkpoint inhibitors has significantly modulated the field of cancer therapies. Testicular DLBCL (T-DLBCL) is presented in an immune-privileged site of the testis, and the roles of NF-kappa B pathway signaling, 9p24.1 aberrations, and tumor-infiltrating immune cells, especially immune checkpoint expressing lymphocytes and macrophages, seem to be unique compared to other lymphoma entities. Preliminary data on the use of immune checkpoint inhibitors in the treatment of T-DLBCL are promising and more studies are ongoing.