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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

Pinheiro, D Y; Chang, Y M; Bryant, H; Szladovits, B; Dalessandri, T; Davison, L J; Yallop, E; Mills, E; Leo, C; Lara, A; Stell, A; Polton, G; Garden, O A

Authors

D Y Pinheiro

Y M Chang

H Bryant

B Szladovits

T Dalessandri

L J Davison

E Yallop

E Mills

C Leo

A Lara

A Stell

G Polton

O A Garden



Abstract

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.

Citation

Pinheiro, D. Y., Chang, Y. M., Bryant, H., Szladovits, B., Dalessandri, T., Davison, L. J., …Garden, O. A. (2014). 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, 9(8), e105027. https://doi.org/10.1371/journal.pone.0105027

Journal Article Type Article
Acceptance Date Jul 19, 2014
Publication Date Aug 13, 2014
Deposit Date Nov 11, 2014
Publicly Available Date Mar 28, 2024
Journal PLoS One
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 8
Pages e105027
DOI https://doi.org/10.1371/journal.pone.0105027
Public URL https://rvc-repository.worktribe.com/output/1405026
Additional Information Corporate Creators : North Downs Referrals, Oxford

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