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PLoS One. 2014 Aug 13;9(8):e105027. doi: 10.1371/journal.pone.0105027. eCollection 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.

Author information

1
Department of Clinical Sciences and Services, Immune Regulation Laboratory, The Royal Veterinary College, London, United Kingdom.
2
Research Office, The Royal Veterinary College, London, United Kingdom.
3
Department of Pathology and Pathogen Biology, The Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.
4
Henry Wellcome Building, Centre for Cellular and Molecular Physiology, University of Oxford, Oxford, United Kingdom; Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
5
Clinical Investigation Centre, The Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.
6
Department of Clinical Sciences and Services, Queen Mother Hospital for Animals, The Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.
7
Oncology Service, North Downs Specialist Referrals, Bletchingley, Surrey, United Kingdom.
8
Department of Clinical Sciences and Services, Immune Regulation Laboratory, The Royal Veterinary College, London, United Kingdom; Department of Clinical Sciences and Services, Queen Mother Hospital for Animals, The Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom.

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.

PMID:
25119018
PMCID:
PMC4132014
DOI:
10.1371/journal.pone.0105027
[Indexed for MEDLINE]
Free PMC Article

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