Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.
The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role i...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0105027 |
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| author | Dammy Pinheiro Yu-Mei Chang Hannah Bryant Balazs Szladovits Tim Dalessandri Lucy J Davison Elizabeth Yallop Emily Mills Chiara Leo Ana Lara Anneliese Stell Gerry Polton Oliver A Garden |
| author_facet | Dammy Pinheiro Yu-Mei Chang Hannah Bryant Balazs Szladovits Tim Dalessandri Lucy J Davison Elizabeth Yallop Emily Mills Chiara Leo Ana Lara Anneliese Stell Gerry Polton Oliver A Garden |
| author_sort | Dammy Pinheiro |
| collection | DOAJ |
| description | The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms. |
| format | Article |
| id | doaj-art-7e8aab657afb416f907f2b635c2fc90e |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7e8aab657afb416f907f2b635c2fc90e2025-08-20T03:46:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10502710.1371/journal.pone.0105027Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.Dammy PinheiroYu-Mei ChangHannah BryantBalazs SzladovitsTim DalessandriLucy J DavisonElizabeth YallopEmily MillsChiara LeoAna LaraAnneliese StellGerry PoltonOliver A GardenThe cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.https://doi.org/10.1371/journal.pone.0105027 |
| spellingShingle | Dammy Pinheiro Yu-Mei Chang Hannah Bryant Balazs Szladovits Tim Dalessandri Lucy J Davison Elizabeth Yallop Emily Mills Chiara Leo Ana Lara Anneliese Stell Gerry Polton Oliver A Garden Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. PLoS ONE |
| title | Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. |
| title_full | Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. |
| title_fullStr | Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. |
| title_full_unstemmed | Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. |
| title_short | Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. |
| title_sort | dissecting the regulatory microenvironment of a large animal model of non hodgkin lymphoma evidence of a negative prognostic impact of foxp3 t cells in canine b cell lymphoma |
| url | https://doi.org/10.1371/journal.pone.0105027 |
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