Adverse prognostic impact of regulatory T-cells in testicular diffuse large B-cell lymphoma

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http://hdl.handle.net/10138/332255

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Pollari , M , Pellinen , T , Karjalainen-Lindsberg , M-L , Kellokumpu-Lehtinen , P-L , Leivonen , S-K & Leppä , S 2020 , ' Adverse prognostic impact of regulatory T-cells in testicular diffuse large B-cell lymphoma ' , European Journal of Haematology , vol. 105 , no. 6 , pp. 712-721 . https://doi.org/10.1111/ejh.13484

Titel: Adverse prognostic impact of regulatory T-cells in testicular diffuse large B-cell lymphoma
Författare: Pollari, Marjukka; Pellinen, Teijo; Karjalainen-Lindsberg, Marja-Liisa; Kellokumpu-Lehtinen, Pirkko-Liisa; Leivonen, Suvi-Katri; Leppä, Sirpa
Upphovmannens organisation: Research Programs Unit
Faculty of Medicine
University of Helsinki
Precision Systems Medicine
Institute for Molecular Medicine Finland
HUS Comprehensive Cancer Center
Medicum
Department of Pathology
Helsinki University Hospital Area
Genome-Scale Biology (GSB) Research Program
Department of Oncology
Clinicum
Digital Precision Cancer Medicine (iCAN)
Datum: 2020-12
Språk: eng
Sidantal: 10
Tillhör serie: European Journal of Haematology
ISSN: 0902-4441
DOI: https://doi.org/10.1111/ejh.13484
Permanenta länken (URI): http://hdl.handle.net/10138/332255
Abstrakt: 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.
Subject: lymphoma
regulatory T-cell
testicular diffuse large B-cell lymphoma
tumor-infiltrating lymphocyte
CENTRAL-NERVOUS-SYSTEM
CLASS-II EXPRESSION
TUMOR MICROENVIRONMENT
TRANSCRIPTION FACTOR
FEATURES
HODGKIN
PD-1
BET
TOLERANCE
BLOCKADE
3122 Cancers
Referentgranskad: Ja
Användningsbegränsning: openAccess
Parallelpublicerad version: acceptedVersion


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