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

Abstract

In the present study, the ability of lymphokines (MAF and IFN gamma) and microbial agents (CP and LM) to induce and maintain tumoricidal activity in BMMP in vitro and to enhance local resistance to the DA rat D-12 ascites tumor in vivo was assessed comparatively. Under standard conditions in vitro, i.e., when present during the 24-hr induction and the 36-hr effector phase, both lymphokines and microbes were similarly potent for eliciting tumoricidal activity in BMMP. When the activating agents were present only during the induction phase, and effector cells were interacted with tumor targets after a 24-hr interval, clear differences were observed: BMMP which had been incubated with lymphokines had largely if not completely lost their tumoricidal activity; in contrast, BMMP which had been incubated with microbes still manifested considerable tumoricidal activity. Experiments performed to assess the in vivo significance of the discrepancy established in vitro have shown that resistance to the D-12 ascites tumor was markedly enhanced after local inoculation of microbes but was affected very little or not at all by soluble lymphokines. The causes responsible for the discrepancy in the antitumor potential of lymphokines vs. microbes are probably manifold. Extensive attempts to improve the efficacy of lymphokines by repeated administration or by incorporation into liposomes were not successful.

Resistance to a non‐immunogenic tumor, induced by Corynebacterium parvum or Listeria monocytogenes, is abrogated by anti‐interferonγ

“…administration of silica particles or carrageenan, suggesting a key role for natural mechanisms, in particular MP. Results of the present experiments showing that immunization with irradiated D-12 cells did not, in any case, enhance resistance to subsequent challenge with live D-12 tumor cells (Table I), support the notion that this tumor is non-immunogenic and that T cells do not play a ma.jor role in resistance against this tumor; they are thus in keeping with various earlier findings (Keller, 1982(Keller, , 1985Keller and Hess, 1982;Keller et al, 1989). The results also indicate that enhancement of tumor resistance by microbial agents remains restricted to the compartment into which these agents had been injected, and represents a strictly local phenomenon.…”

Induction and Activation of Tumoricidal Cells In Vivo and In Vitro by the Bacterial Cell Wall of Bifidobacterium infantis

“…To determine which kinds of immune cells commit to these tumor rejection activities, we analyzed the kinetics of peritoneal and thoracic exudate cells after a single WPG injection. As predicted from the studies of others using bacterial preparations, PMNs and then macrophages were massively induced at the sites of WPG injection (7,14,20). The results were corroborated with the previous study by Tsuyuki et al (31) using a subcutaneous WPG injection.…”

Surface phenotype of rat bone marrow-derived mononuclear phagocytes

“…PGE, and polymyxin B sulfate were from Sigma, St. Louis, MO. Corynebacterium pawurn (CP; ATCC 6916) organisms were cultured and heatkilled as described by Keller et al (1989b).…”