Transient downregulation of monocyte-derived dendritic-cell differentiation, function, and survival during tumoral progression and regression in an in vivo canine model of transmissible venereal tumor.
Resource
Cancer Immunol Immunother.,57(4),479-491.
Journal
Cancer Immunology Immunotherapy
Pages
479-491
Date Issued
2008-08
Date
2008-08
Author(s)
Liu, C. C
Wang, Y. S.
Lin, C. Y.
Chuang, T. F.
Liao, K. W.
Chi, K. H.
Chen, M. F.
Chiang, H. C.
Chu, R. M.
Abstract
Tumors often target dendritic cells (DCs) to evade host immune surveillance. DC injury is reported in many rodent and human tumors but seldom in tumors of other mammals. Canine transmissible venereal tumor (CTVT), a unique and spontaneous cancer transmitted by means of viable tumor cells. CTVT causes manifold damage to monocyte-derived DCs. This cancer provides an in vivo model of cancer to study the role of monocyte-derived DCs during spontaneous regression. Using flow cytometry and real-time reverse-transcription polymerase chain reactions, we compared the expression of surface molecules on monocyte-derived DCs between normal dogs and dogs with CTVT. These markers were CD1a, CD83, costimulatory factors (CD40, CD80, and CD86), and major histocompatability complex classes I and II. In immature DCs (iDCs) and lipopolysaccharide-treated mature DCs (mDCs), the surface markers were mostly downregulated during tumoral progression and regression. The tumor lowered endocytic activity of iDCs, as reflected in dextran uptake, and decreased allogeneic mixed lymphocyte reactions of mDCs. In addition, it decreased the number of monocytes in the peripheral blood by 40%. The tumor substantially impaired the efficiency with which DCs were generated from monocytes and with which mDCs were generated from iDCs. We also found that progression-phase CTVT supernatants that were cultured for 48 h and that contained protein components killed both monocytes and DCs. Additionally, DC numbers were significantly lower in the draining lymph nodes in CTVT dogs than in normal dogs. In conclusion, CTVT caused devastating damage to monocyte-derived DCs; this might be one of its mechanisms for evading host immunity. Reestablishment of monocyte-derived DC activity by the host potentially might contribute to spontaneous tumoral regression. These findings provide insight into the extent of tumoral effects on host immune systems and responses. This information is useful for developing cancer immunotherapies. ? 2007 Springer-Verlag.
SDGs
Other Subjects
B7 antigen; biological marker; CD40 antigen; CD83 antigen; CD86 antigen; HLA antigen class 1; HLA antigen class 2; lipopolysaccharide; membrane protein; monoclonal antibody; t6 antigen; animal cell; animal venereal tumor; article; cancer growth; cancer regression; cell activity; cell culture; cell differentiation; cell function; cell maturation; cell survival; cell viability; cellular immunity; controlled study; dendritic cell; dog; down regulation; flow cytometry; histocompatibility complex; in vivo study; lymphoid cell line; monocyte; nonhuman; priority journal; protein expression; real time polymerase chain reaction; Animals; Antigens, CD; Cell Differentiation; Cell Survival; Dendritic Cells; Disease Models, Animal; Disease Progression; Dog Diseases; Dogs; Down-Regulation; Flow Cytometry; Histocompatibility Antigens; Humans; Lymphocyte Culture Test, Mixed; Lymphocytes, Tumor-Infiltrating; Monocytes; Reverse Transcriptase Polymerase Chain Reaction; Tumor Escape; Venereal Tumors, Veterinary
Type
journal article