Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas
The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular DLBCLs (T-DLBCL) using gene express...
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| Format: | Article |
| Language: | English |
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Ferrata Storti Foundation
2024-12-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11869 |
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| author | Matias Autio Oscar Brück Marjukka Pollari Marja-Liisa Karjalainen-Lindsberg Klaus Beiske Judit Mészaros Jørgensen Harald Holte Teijo Pellinen Suvi-Katri Leivonen Sirpa Leppä |
| author_facet | Matias Autio Oscar Brück Marjukka Pollari Marja-Liisa Karjalainen-Lindsberg Klaus Beiske Judit Mészaros Jørgensen Harald Holte Teijo Pellinen Suvi-Katri Leivonen Sirpa Leppä |
| author_sort | Matias Autio |
| collection | DOAJ |
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The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular DLBCLs (T-DLBCL) using gene expression profiling and multiplex immunohistochemistry. We found that high proportions of M2-like tumor-associated macrophages (TAMs) and cytotoxic tumor-infiltrating T cells (TILs) were characteristic of ABC DLBCL TME. Furthermore, high CD8+ TIL content translated to favorable outcomes. In contrast, GCB DLBCL TME was enriched in CD4+ TILs, regulatory TILs, and a higher M1-like/M2-like TAM ratio, and high proportions of TAMs and Granzyme B+ cells associated with worse survival. TILs and TAMs interacted more frequently with M2-like TAMs and cytotoxic TILs in the ABC DLBCLs contrary to GCB subtype, where the interactions were more abundant with other TILs and CD4+ TILs. In T-DLBCL, TME resembled that of ABC DLBCL with a higher proportion of M2-like TAMs and cytotoxic cells, except that checkpoint-positive TILs were less prominent compared to DLBCL NOS. Cytotoxic TILs also interacted more with TILs and TAMs. A high amount of CD163+ TAM interactions with distinct TILs translated to unfavorable survival both in GCB DLBCL and T-DLBCL, whereas a high number of interactions between TILs and TAMs, CD4+ TILs and TAMs, and CD4+ TILs and other TILs associated with favorable outcomes only in T-DLBCL. Together, our data demonstrate biologically and clinically relevant differences in the composition of and cellular interactions in the TME between various DLBCL entities.
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| format | Article |
| id | doaj-art-cc01ced79bf645829d71f227d8145e74 |
| institution | OA Journals |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-cc01ced79bf645829d71f227d8145e742025-08-20T01:59:04ZengFerrata Storti FoundationHaematologica0390-60781592-87212024-12-01999110.3324/haematol.2024.286267Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomasMatias Autio0Oscar Brück1Marjukka Pollari2Marja-Liisa Karjalainen-Lindsberg3Klaus Beiske4Judit Mészaros Jørgensen5Harald Holte6Teijo Pellinen7Suvi-Katri Leivonen8Sirpa Leppä9Research Programs Unit, Applied Tumor Genomics, University of Helsinki, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Medicine Flagship, HelsinkiHematoscope Lab, Comprehensive Cancer Center and Center of Diagnostics, Helsinki University Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki, HelsinkiResearch Programs Unit, Applied Tumor Genomics, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Medicine Flagship, Helsinki, Finland; Department of Oncology, Tampere University Hospital, TampereDepartment of Pathology, Helsinki University Hospital, HelsinkiDepartment of Pathology, Oslo University Hospital, OsloDepartment of Hematology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology, and KG Jebsen Centre for B cell malignancies, Oslo University Hospital, OsloInstitute for Molecular Medicine Finland (FIMM), HelsinkiResearch Programs Unit, Applied Tumor Genomics, University of Helsinki, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Medicine Flagship, HelsinkiResearch Programs Unit, Applied Tumor Genomics, University of Helsinki, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; iCAN Digital Precision Medicine Flagship, Helsinki The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular DLBCLs (T-DLBCL) using gene expression profiling and multiplex immunohistochemistry. We found that high proportions of M2-like tumor-associated macrophages (TAMs) and cytotoxic tumor-infiltrating T cells (TILs) were characteristic of ABC DLBCL TME. Furthermore, high CD8+ TIL content translated to favorable outcomes. In contrast, GCB DLBCL TME was enriched in CD4+ TILs, regulatory TILs, and a higher M1-like/M2-like TAM ratio, and high proportions of TAMs and Granzyme B+ cells associated with worse survival. TILs and TAMs interacted more frequently with M2-like TAMs and cytotoxic TILs in the ABC DLBCLs contrary to GCB subtype, where the interactions were more abundant with other TILs and CD4+ TILs. In T-DLBCL, TME resembled that of ABC DLBCL with a higher proportion of M2-like TAMs and cytotoxic cells, except that checkpoint-positive TILs were less prominent compared to DLBCL NOS. Cytotoxic TILs also interacted more with TILs and TAMs. A high amount of CD163+ TAM interactions with distinct TILs translated to unfavorable survival both in GCB DLBCL and T-DLBCL, whereas a high number of interactions between TILs and TAMs, CD4+ TILs and TAMs, and CD4+ TILs and other TILs associated with favorable outcomes only in T-DLBCL. Together, our data demonstrate biologically and clinically relevant differences in the composition of and cellular interactions in the TME between various DLBCL entities. https://haematologica.org/article/view/11869 |
| spellingShingle | Matias Autio Oscar Brück Marjukka Pollari Marja-Liisa Karjalainen-Lindsberg Klaus Beiske Judit Mészaros Jørgensen Harald Holte Teijo Pellinen Suvi-Katri Leivonen Sirpa Leppä Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas Haematologica |
| title | Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas |
| title_full | Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas |
| title_fullStr | Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas |
| title_full_unstemmed | Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas |
| title_short | Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas |
| title_sort | characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large b cell lymphomas |
| url | https://haematologica.org/article/view/11869 |
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