Abstract
BackgroundSpontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression.MethodsHens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis.ResultsT and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors.ConclusionsThe results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials.
Highlights
Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically
A higher tumor content of CD3+ T cells [3] or CD8+ cytotoxic T cells [4] in late stage tumors is associated with a better prognosis for ovarian cancer patients while a higher relative content of T regulatory cells is associated with a poorer prognosis [5], suggesting the number and types of immune cells are important for clinical outcomes
Recent evidence suggests that CD20+ B cells are found in both early and late stage ovarian tumors and that higher numbers may be related to better five year survival rates [6]
Summary
Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. A higher tumor content of CD3+ T cells [3] or CD8+ cytotoxic T cells [4] in late stage tumors is associated with a better prognosis for ovarian cancer patients while a higher relative content of T regulatory cells is associated with a poorer prognosis [5], suggesting the number and types of immune cells are important for clinical outcomes. Recent evidence suggests that CD20+ B cells are found in both early and late stage ovarian tumors and that higher numbers may be related to better five year survival rates [6]. Further development of pre-clinical models of ovarian cancer is needed to facilitate development and testing of vaccines to treat ovarian cancer
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