Host-tumor interactions during the regression of a rat histiocytoma, AK-5

An efficient immune response comprises a highly intricate, integrated circuitry involving both the cellular and the humoral arms of the immune system of the host interacting with the rapidly proliferating microcosm of the tumor The mechanism of tumor rejection involving multiple arms of the immune system was reviewed in a spontaneously regressing rat histiocytoma, AK-5, an autologous tumor-host system. Intraperitoneal tumor transplantation leads to death in all animals, whereas subcutaneously (s.c.) transplanted tumor undergoes regression in 70% of animals. Regression of the tumor occurs by both apoptosis and necrosis, and natural killer (NK) cells were identified as the chief effectors mediating tumor cell death in vivo. A type 1 helper T cell (Th1)-driven cytokine cascade played a crucial role in enhancing cellular functions at the tumor site and obtaining a sufficient immune response for tumor rejection. The s.c. tumor-bearing hosts were shown to produce a factor which induced apoptosis in tumor cells, mediating tumor rejection. This review emphasizes the daunting complexities and interesting liaisons between the host immune system and the tumor, highlighting the work from our laboratory, and stressing that it is the interaction of several factors in concert or antagonizing each other that is responsible for the spontaneous regression of a tumor.