Tumor-specific immunological and pathological changes in layer chickens affected with ovarian adenocarcinoma

Human epithelial ovarian cancer (EOC) is characterized by profound immune dysregulation with a tumor microenvironment (TME) dominated by immunosuppressive populations such as regulatory T-cells that actively limit anti-tumor responses. Spontaneous ovarian tumors in older laying hens (Gallus gallus domesticus) closely resemble human EOC development and histopathological features, making them an ideal model to study human EOC. Here, we examined pathological and immunological changes in ovarian TME from hens with spontaneous ovarian tumors (OT). Histopathological characterization was consistent with the endometrioid subtype of ovarian adenocarcinoma, while the immunohistochemistry analysis showed reduced intratumoral T cell infiltration compared to control. The OT tissue gene expression analysis showed significant upregulation of FoxP3, CD25, CD40, PD-1, LAG-3 and GITR genes, accompanied by an increased IL-10 transcription compared to control, indicating regulatory T cell expansion and effector T cell exhaustion. Furthermore, significant reduction in the IL-1β, chTNFα and iNOS transcription suggested suppressed cellular inflammatory activation. These findings demonstrate that ovarian tumors in laying hens undergo a transition from an inflammatory state to an immunoregulatory, checkpoint-dominant TME, an observation resembling human EOC. This work supports the laying hen as a translational model for studying human ovarian cancer and developing diagnostic and therapeutic strategies.