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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

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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.

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Acknowledgments

This research was supported by the National Science Council, Taiwan, ROC (NSC 95-2323-B-002-025).

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Authors and Affiliations

  1. Department of Veterinary Medicine, Animal Cancer Research Center, National Taiwan University, 1, Roosevelt Road, Section 4, 106, Taipei, Taiwan, ROC

    Cheng-Chi Liu, Yu-Shan Wang, Ching-Yi Lin, Tien-Fu Chuang, Mo-Fan Chen, Hsin-Chien Chiang & Rea-Min Chu

  2. Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC

    Yu-Shan Wang & Kwan-Hwa Chi

  3. Department of Biological Sciences and Technology, College of Life Sciences, Hsin-Chu, Taiwan, ROC

    Kuang-Wen Liao

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  1. Cheng-Chi Liu
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  2. Yu-Shan Wang
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Correspondence to Rea-Min Chu.

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C.-C. Liu and Y.-S. Wang contributed equally.

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Liu, CC., Wang, YS., Lin, CY. et al. 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. Cancer Immunol Immunother 57, 479–491 (2008). https://doi.org/10.1007/s00262-007-0386-0

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