@article { , 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}, 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; pā€Š=ā€Š0.01) and overall survival (hazard ratio 1.61; pā€Š=ā€Š0.01) 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.}, doi = {10.1371/journal.pone.0105027}, issue = {8}, journal = {PLoS One}, pages = {e105027}, publicationstatus = {Published}, publisher = {Public Library of Science}, url = {https://rvc-repository.worktribe.com/output/1405026}, volume = {9}, keyword = {ePrints migration}, year = {2014}, author = {Pinheiro, D Y and Chang, Y M and Bryant, H and Szladovits, B and Dalessandri, T and Davison, L J and Yallop, E and Mills, E and Leo, C and Lara, A and Stell, A and Polton, G and Garden, O A} }