Decreased Ratio of CD8+ T Cells to Regulatory T Cells Associated with Decreased Survival in Dogs with Osteosarcoma

被引:83
作者
Biller, B. J. [1 ]
Guth, A. [1 ]
Burton, H. [1 ]
Dow, S. W. [1 ]
机构
[1] Colorado State Univ, Dept Clin Sci, Anim Canc Ctr, Ft Collins, CO 80523 USA
关键词
Canine; Lymphocyte; Neoplasia; Prognosis; TUMOR-IMMUNITY; ANTITUMOR IMMUNITY; CANCER-PATIENTS; OVARIAN-CANCER; FOXP3; LYMPHOCYTES; EXPRESSION; CHEMOTHERAPY; INFECTION; CARCINOMA;
D O I
10.1111/j.1939-1676.2010.0557.x
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Background Increased numbers of regulatory T cells (Treg) and decreased ratios of CD8+ T cells to Treg have been shown to correlate with decreased survival times (ST) in humans with certain malignancies. A possible connection between Treg and ST in dogs with cancer has not been investigated previously. Hypothesis The purpose of this study was to compare numbers of Treg and T lymphocyte subsets in dogs with osteosarcoma (OSA) to those of healthy dogs and to determine whether pretreatment values were associated with disease-free interval or with ST. We hypothesized that Treg numbers would be increased in dogs with cancer and that dogs with a high percentage of Treg would have a poorer prognosis. Animals Twelve client-owned dogs with appendicular OSA were entered into a prospective clinical trial. Twenty-two healthy dogs were used as controls. Methods The percentages and numbers of Treg and CD4+ and CD8+ T cells in blood, lymph nodes, and tumors were determined with flow cytometry and compared between dogs with OSA and control dogs. Results Dogs with OSA had significantly fewer circulating CD8+ T cells and significantly more Treg compared with healthy dogs. The CD8/Treg ratio also was significantly lower in dogs with OSA compared with control dogs. In dogs with OSA, a decreased CD8/Treg ratio was associated with significantly shorter STs. Conclusions These data support a role for Treg in the immune control of canine OSA and suggest that determination of the CD8/Treg ratio may be useful for assessing outcomes.
引用
收藏
页码:1118 / 1123
页数:6
相关论文
共 33 条
[1]   Use of alternating administration of carboplatin and doxorubicin in dogs with microscopic metastases after amputation for appendicular osteosarcoma: 50 cases (1999-2006) [J].
Bacon, Nicholas J. ;
Ehrhart, Nicole R. ;
Dernell, William S. ;
Lafferty, Mary ;
Withrow, Stephen J. .
JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION, 2008, 232 (10) :1504-1510
[2]   Regulatory cells and human cancer [J].
Baecher-Allan, C ;
Anderson, DE .
SEMINARS IN CANCER BIOLOGY, 2006, 16 (02) :98-105
[3]   Differences in immune cells engaged in cell-mediated immunity after chemotherapy for far advanced pancreatic cancer [J].
Bang, S ;
Kim, HS ;
Choo, YS ;
Park, SW ;
Chung, JB ;
Song, SY .
PANCREAS, 2006, 32 (01) :29-36
[4]   Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer [J].
Biller, B. J. ;
Elmslie, R. E. ;
Burnett, R. C. ;
Avery, A. C. ;
Dow, S. W. .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2007, 116 (1-2) :69-78
[5]   Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck [J].
Boucek, Jan ;
Mrkvan, Tomas ;
Chovanec, Martin ;
Kuchar, Martin ;
Betka, Jaroslav ;
Boucek, Vladimir ;
Hladikova, Marie ;
Betka, Jan ;
Eckschlager, Tomas ;
Rihova, Blanka .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2010, 14 (1-2) :426-433
[6]   A high proportion of bone marrow T cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease [J].
Brinkrolf, Peter ;
Landmeier, Silke ;
Altvater, Bianca ;
Chen, Christiane ;
Pscherer, Sibylle ;
Rosemann, Annegret ;
Ranft, Andreas ;
Dirksen, Uta ;
Juergens, Heribert ;
Rossig, Claudia .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (04) :879-886
[7]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[8]   Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells [J].
Dannull, J ;
Su, Z ;
Rizzieri, D ;
Yang, BK ;
Coleman, D ;
Yancey, D ;
Zhang, AJ ;
Dahm, P ;
Chao, N ;
Gilboa, E ;
Vieweg, J .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (12) :3623-3633
[9]   Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice [J].
Darrasse-Jeze, Guillaume ;
Bergot, Anne-Sophie ;
Durgeau, Aurelie ;
Billiard, Fabienne ;
Salomon, Benoit L. ;
Cohen, Jose L. ;
Bellier, Bertrand ;
Podsypanina, Katrina ;
Klatzmann, David .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (09) :2648-2662
[10]   Lymphocyte subsets in peripheral blood of dogs -: a flow cytometric study [J].
Faldyna, M ;
Levá, L ;
Knötigová, P ;
Toman, M .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2001, 82 (1-2) :23-37