Autochthonous murine tumors: Effects of viral or ultraviolet induction, immunogenicity and transplantation on intratumoral macrophages and systemic inflammatory responses

Abstract

Macrophage tumoricidal activity requires a constant influx of macrophages but many transplanted cancers inhibit macrophage inflammatory responses. In this paper we address the issue of whether or not autochthonous tumors induced by either mammary tumor virus (MTV) in C3H/He mice or ultraviolet (u.v.) radiation in C3H/He or BALB/c mice also depress macrophage responses. Anti-inflammatory activity was not observed either prior to or during growth of these autochthonous tumors. Rather, the opposite was observed: strongly immunogenic u.v.-induced tumors which were rejected upon transplantation to syngeneic hosts had enhanced macrophage responses and more intratumoral macrophages than those mice whose tumors were transplantable. Transplantation of MTV-induced tumors selected for more aggressive tumors which had fewer intratumoral macrophages. In both MTV- and u.v.-induced tumors inflammatory responses of mice bearing serially transplanted tumors often differed from mice with autochthonous tumors. Our results demonstrate that anti-inflammation is probably not required for emergence and growth of these autochthonous tumors, that strongly immunogenic tumors may actually enhance macrophage responses and that the effect of tumor bearing on macrophage inflammation is a characteristic of the tumor, including its site and host of origin, its immunogenicity and its transplant generation.