Interdependence of macrophages and T-cells in partial spontaneous regression of intrahepatic cholangiocarcinoma in a cow: a histopathologic perspective

Viewed from clinical, pathologic, and therapeutic perspectives, an understanding of spontaneous regression of tumors, a specific aspect of tumor biology, may be important to both medical and veterinary science. This naturally occurring regressive phenomenon of tumors is associated with a wide variety of pathophysiologic mechanisms. The function and kinetics of immune cells in the development of partial spontaneous regression in intrahepatic cholangiocarcinoma of a cow was evaluated. Histopathologic and immunohistochemical investigations of anti-tumor activities performed by immune cells (macrophages and lymphocytes) were conducted on a cow that presented with partially regressing intrahepatic cholangiocarcinoma on postmortem examination. Apart from showing multifocal coagulative necrosis concurrent with hemorrhagic changes, the cancer frequently represented discrete areas that demonstrated regressing features, characterized by unequivocal collapse of cancer cell nests, closely associated with a significant infiltration of macrophages (i.e., professional phagocytes possessing phagosomes or phagolysosomes) and lymphocytes (T-cells) in a well-developed, surrounding desmoplastic stroma; characteristically, the more intense the macrophage and T-cell infiltration, the heavier the damage to cancer cell nests. Other still progressing lesions of the cancer often had an intrastromal infiltration of moderate numbers of T-cells. Viewed from an immune-cell functional and kinetic perspective, most likely the initial event was appearance of T-cells in the tumor microenvironment, later followed by the migration of macrophages, thereby the interdependence of these 2 cell types likely exserted an anti-cancer effect efficiently, giving rise to partial spontaneous regression of this hepatic malignancy.