Inflammatory changes after cryosurgery-induced necrosis in human melanoma xenografted in nude mice

There is growing evidence that necrosis, instead of apoptosis, could act as a natural adjuvant, which could activate an immune response. In this work we have investigated if induction of tumor necrosis could trigger the afflu ence of inflammatory cells at the tumor site, and thus induce an immune res ponse. For this purpose, a Liquid N-2 spray was applied on human melanoma ( IIB-MEL-J cell line) xenografted in nude mice and 24 h later some mice rece ived intratumorally a single 500 U dose of recombinant murine granulocyte m acrophage-colony-stimulating factor. 77-100% of the turner mass underwent n ecrosis. Congestion, edema, and endothelial cell activation were the first noticeable events. A quick infiltrative response of polymorphonuclear leuko cytes around the tumor was detected 24 h after liquid N-2 application, peak ing at day 3, Massive macrophage recruitment was observed since day 3. An e arly intratumoral infiltration with inflammatory cells was only detected in the group that received recombinant murine granulocyte macrophage-colony-s timulating factor after necrosis induction by liquid N-2. Coexisting DEC 20 5- and F4/80-positive cells increased in number, and their localization was predominantly peritumoral after necrosis. Antibody response was only detec ted in the groups with tumor-induced necrosis. Our results suggest that cry osurgery-induced necrosis could be a useful model to analyze the interactio n among necrosis, inflammation, and the generation of an immune response.