Changes in regulatory T cells in dogs with B-cell lymphoma and association with clinical tumour stage
Baek DS, Chung TH, Kim YH, Oh SK, So KM, Park Chttps://doi.org/10.17221/7/2015-VETMEDCitation:Baek DS, Chung TH, Kim YH, Oh SK, So KM, Park C (2017): Changes in regulatory T cells in dogs with B-cell lymphoma and association with clinical tumour stage. Veterinarni Medicina, 62: 647-653.
Among several mechanisms that allow tumours to disarm the host immune system and thus to evade or suppress protective anti-tumour immunity, an important role for CD4+CD25+FoxP3+ regulatory T cells (Tregs) has emerged. Numerous studies in humans have demonstrated increased Tregs in patients with carcinomas of the breast, lung, and pancreas, and this increased Treg has been correlated with poor prognosis. This study was performed (1) to investigate the percentage of Tregs in total lymphocytes of the peripheral blood in 12 canine patients with B cell lymphoma and (2) to investigate the change in the percentage of Tregs in canine lymphoma of different clinical tumour stages. On the flow cytometric analysis, the relative and absolute numbers of Tregs were significantly increased in 12 canine patients with B-cell lymphoma compared to five healthy beagles included in this study, and the greatest increases in the relative and absolute number of Tregs occurred in two dogs with more advanced World Health Organization clinical stages with bone marrow involvement compared to those in less advanced tumour stages without bone marrow involvement. This study provides basic information regarding the negative role of Treg recruitment in canine lymphoma patients and highlights the potential value of Treg levels as prognostic indicators in canine cancer patients.Keywords:
cancer; regulatory T cell; Treg; canine lymphoma; immune escape; WHO clinical tumour stagesReferences:
Beyer M. (2006): Regulatory T cells in cancer. Blood, 108, 804-811 https://doi.org/10.1182/blood-2006-02-002774Biller B.J., Elmslie R.E., Burnett R.C., Avery A.C., Dow S.W. (2007): Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer. Veterinary Immunology and Immunopathology, 116, 69-78 https://doi.org/10.1016/j.vetimm.2006.12.002Burnet F. M. (1971): Immunological Surveillance in Neoplasia. Immunological Reviews, 7, 3-25 https://doi.org/10.1111/j.1600-065X.1971.tb00461.xCuriel Tyler J, Coukos George, Zou Linhua, Alvarez Xavier, Cheng Pui, Mottram Peter, Evdemon-Hogan Melina, Conejo-Garcia Jose R, Zhang Lin, Burow Matthew, Zhu Yun, Wei Shuang, Kryczek Ilona, Daniel Ben, Gordon Alan, Myers Leann, Lackner Andrew, Disis Mary L, Knutson Keith L, Chen Lieping, Zou Weiping (2004): Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Medicine, 10, 942-949 https://doi.org/10.1038/nm1093Dunn Gavin P., Bruce Allen T., Ikeda Hiroaki, Old Lloyd J., Schreiber Robert D. (): Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunology, 3, 991-998 https://doi.org/10.1038/ni1102-991Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, Sakaguchi S (1999): Thymus and autoimmunity: Production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. The Journal of Immunology 162, 5317–5326.Koebel Catherine M., Vermi William, Swann Jeremy B., Zerafa Nadeen, Rodig Scott J., Old Lloyd J., Smyth Mark J., Schreiber Robert D. (2007): Adaptive immunity maintains occult cancer in an equilibrium state. Nature, 450, 903-907 https://doi.org/10.1038/nature06309Mukherjee P, Ginardi AR, Madsen CS, Tinder TL, Jacobs F, Parker J, Agrawal B, Longenecker BM, Gendler SJ (2001): MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment. Glycoconjugate Journal 18, 931–942.https://doi.org/10.1023/A:1022260711583O'Neill K., Guth A., Biller B., Elmslie R., Dow S. (2009): Changes in Regulatory T Cells in Dogs with Cancer and Associations with Tumor Type. Journal of Veterinary Internal Medicine, 23, 875-881 https://doi.org/10.1111/j.1939-1676.2009.0333.xQuezada Sergio A., Peggs Karl S., Simpson Tyler R., Allison James P. (2011): Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunological Reviews, 241, 104-118 https://doi.org/10.1111/j.1600-065X.2011.01007.xSakaguchi Shimon (2000): Regulatory T Cells. Cell, 101, 455-458 https://doi.org/10.1016/S0092-8674(00)80856-9Sakaguchi Shimon (2005): Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nature Immunology, 6, 345-352 https://doi.org/10.1038/ni1178Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995): Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of Immunology 155, 1151–1164.Sasada Tetsuro, Kimura Motohide, Yoshida Yuka, Kanai Michiyuki, Takabayashi Arimichi (2003): CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies. Cancer, 98, 1089-1099 https://doi.org/10.1002/cncr.11618Shevach EM (2002): CD4+CD25+ suppressor T cells: More questions than answers. Nature Reviews Immunology 2, 389–400.Terme Magali, Ullrich Evelyn, Delahaye Nicolas F, Chaput Nathalie, Zitvogel Laurence (2008): Natural killer cell–directed therapies: moving from unexpected results to successful strategies. Nature Immunology, 9, 486-494 https://doi.org/10.1038/ni1580Viguier M., Lemaitre F., Verola O., Cho M.-S., Gorochov G., Dubertret L., Bachelez H., Kourilsky P., Ferradini L. (2004): Foxp3 Expressing CD4+CD25high Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells. The Journal of Immunology, 173, 1444-1453 https://doi.org/10.4049/jimmunol.173.2.1444Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B (2003): Increase of regulatory T cells in the peripheral blood of cancer patients. Clinical Cancer Research 9, 606–612.Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH (2001): Regulatory CD4+ CD25+ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Research 61, 4766–4772.Yang S.-C. (2004): Intratumoral Administration of Dendritic Cells Overexpressing CCL21 Generates Systemic Antitumor Responses and Confers Tumor Immunity. Clinical Cancer Research, 10, 2891-2901 https://doi.org/10.1158/1078-0432.CCR-03-0380