Cell-mediated immunity and expression of MHC class I and class II molecules in dogs naturally infected by canine transmissible venereal tumor: Is there complete spontaneous regression outside the experimental CTVT?

The canine transmissible venereal tumor (CTVT) is a transplantable cancer with the ability evade the immune system, despite strict immune surveillance of the host; in this context, the relationship between inflammatory infiltrate and CTVT prognosis is not entirely understood. Natural canine transmissible venereal tumors of 22 dogs were evaluated for tumor/host interaction through clinical and epidemiological data, cyto-histopathological and cytogenetic findings and, mainly, cell-mediated immune response. We performed analysis on dogs with naturally acquired disease to provide information from the study of CTVT biology in its natural course, as the clinical evolution of the natural tumor in the host is not yet as well known as in the laboratory. Populations for T cell labeling (CD3+ CD4+ CD8+), B cells, NK cells, and macrophages were analyzed by flow cytometry in blood and tumor samples and expressions of MHC class I and class II molecules were quantified by immunohistochemistry and compared mainly between the phases of progression and regression in the natural CTVT. Dogs were also treated with vincristine sulfate and evaluated for chemotherapeutic response. Chemotherapy was effective in 88% of cases and there was no recurrence of the disease 12 months after the cure. Tumor cells displayed a numerical chromosomal variation between 54 and 72, not correlating with the host genotype. Although a greater expression of MHC molecules [18.6 ± 5.8% class I (P < 0.004) and 38.5 ± 6.5% class II (P < 0.003)] was observed in the regression phase, no significant effect was observed between the clinical phase of the tumor and cellular immune response in the analysis by flow cytometry (P > 0.05). We also found no correlation between cytological subtype of the tumor (plasmacytoid, lymphocytoid and mixed) and cellular immune response, suggesting that there is no difference in tumor immunogenicity. Here, we found no immunological evidence to support the theory of the immune-induced complete spontaneous regression in CTVT.

do Prado Duzanski A ，Flórez LMM ，Fêo HB ，Romagnoli GG ，Kaneno R ，Rocha NS ... -  《-》

Effect of tumor infiltrating lymphocytes on the expression of MHC molecules in canine transmissible venereal tumor cells.

Hsiao YW ，Liao KW ，Hung SW ，Chu RM ... -  《VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY》

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.

Liu CC ，Wang YS ，Lin CY ，Chuang TF ，Liao KW ，Chi KH ，Chen MF ，Chiang HC ，Chu RM ... -  《-》

Immunohistochemical study of the local inflammatory infiltrate in spontaneous canine transmissible venereal tumour at different stages of growth.

Pérez J ，Day MJ ，Mozos E 《VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY》

Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs?

The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL-6, IFN-γ, and TGF-β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine. As expected, the most prevalent subtype was plasmacytoid cells, although lymphocytic cells were also found, indicating the possibility of polyclonality. When we compared the gene expressions of IFN-γ and IL-6, we mostly found low expression, concluding that MHC expression was probably not occurring in tumour cells, and no activation of immune cells to eliminate the tumour. The TGF-β gene was normal in the majority of animals but demonstrated decreased expression in vincristine resistant animals, leading to the hypothesis that the concentration of tumour-derived TGF-β was affecting and even suppressing the real TGF-β expression, favouring tumour proliferation and progression in these cases. VEGF expression was extremely high, demonstrating its angiogenic role in tumour growth, while CXCR4 was decreased, possibly because of CTVT's low metastatic potential. Thus, we concluded that the tumour microenvironment, together with the immune system of the host, influences CTVT, presumably altering its tumorigenesis and the animal's clinical response to treatment.

Ballestero Fêo H ，Montoya Flórez L ，Yamatogi RS ，Prado Duzanski A ，Araújo JP ，Oliveira RA ，Rocha NS ... -  《-》