Abrogation of Antitumor Effects of Corynebacterium parvum and BeG by Antimacrophage Agents: Brief Communication 2

Abstract

ABSTRACT-The consistently demonstrable antitumor effect of Corynebacterium parvum and BCG against a 7,12-dimethylbenz[aJanthracene-lnduced rat flbrosarcoma, growlng either as a localized subcutaneous tumor or in ascites form, was abrogated by treatment of rats with antlmacrophage agents such as slllca or carrageenan.

Discrepancy in the abilities of lymphokines and bacteria to mediate tumor protection in vivo and/or tumoricidal activity by macrophages in vitro

“…In this experimental tumor model, a tumor inoculum of low size suffices to elicit progressive ascites tumor growth that can be readily quantitated (Keller, 1980~). Moreover, D-12 ascites tumor growth can be easily and reproducibly modulated by a variety of interventions (Keller, 1976(Keller, , 1977. D-12 cells are non-immunogenic and T cells appear to have no direct role in the host's defense against the D-12 tumor (Keller et al, 1971;Keller, 19806, 1982Keller, 19806, , 1985Keller and Hess, 1982).…”

“…These findings further support the concept that, for in vivo induction of host defense against the D-12 tumor by CP and LM, an interval of several days is required, and that the time period around tumor-cell implantation is particularly critical for the outcome of the interaction. As resistance triggered by CP and LM was readily abrogated by anti-macrophage agents, a dominant role for macrophages in the host's defense against this tumor has been postulated (Keller, 1977.…”

“…Earlier work from this laboratory, utilizing the operationally simple and reproducible DA rat D-12 ascites tumor model, has shown that the weak spontaneous local resistance against this tumor can be markedly enhanced by attentuated or heat-killed facultative intracellular pathogens, such as BCG, CP, and/or LM, provided that these agents are inoculated into the same compartment several days before tumor-cell challenge (Keller, 1977. The tumor-protective effect induced by these microbial agents against this non-immunogenic tumor was readily and completely abolished by a variety of agents, e.g., silica particles, carrageenan andlor anti-IFNy, when administered locally several days before tumor-cell challenge (Keller, 1977. These and other findings (Keller et al, 1971) were taken as support for the concept that, in this particular experimental system, local natural mechanisms hold a key role in mediation of the anti-tumor resistance induced by the microbial pathogens.…”

BCG treatment of transplanted rat tumours of spontaneous origin

“…In keeping with these findings, the present studies with both naturally occurring rat sarcomas and mammary carcinomas establish that the capacity of BCG organisms to suppress tumour growth is not dependent upon the innate immunogenicity of the tumour. The host responses initiated when tumour cells are injected in admixture with bacterial preparations such as BCG have not yet been fully characterized, but are thought to require macrophages since tumour suppression does not occur in rats pretreated with silica preparations which selectively deplete phagocytic cells (Chassoux and Salomon, 1975;Keller, 1977;Hopper et al, 1976; Moore and Nisbet, 1978). It has also been established that with MCA-induced sarcomas, where BCG-mediated contact suppression of tumour growth is highly effective, developing tumour masses contain up to 40% of macrophages (Baldwin et al, 1976).…”