title: Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance.
abstract: Interferon-gamma-receptor (IFN-gammaR)-deficient mice are more susceptible to tumor induction by methylcholanthrene (MCA) in comparison to control littermates. The cellular source of IFNgamma is not known, but the absence of T cells does not significantly increase the incidence of MCA-induced tumors. However, it appears that the presence of T cells in combination with unknown, perhaps environmental, factors can decrease MCA-induced tumor incidence, indicating that IFN-gamma of unknown origin contributes to the protective response. The current knowledge of cancer biology, immune regulation, and tumor-promoting effects of inflammation are difficult to reconcile with the concept of immune surveillance against non-virus-associated cancer. Analysis of the primary MCA-treated mouse indicates, as one protective mechanism, a tissue repair response against MCA-induced damage, in the course of which MCA is encapsulated and persists for long time in tumor-free mice, termed foreign-body reaction. The protection from DNA damage could simultaneously diminish tissue injury and malignant transformation. We argue that inhibition of MCA-induced carcinogenesis is mechanistically different from tumor transplantation immunity and that a longer latency in MCA-treated mice is unlikely due to T cell-mediated tumor recognition and selection of less immunogenic variants. We discuss that the IFNgammaR-dependent mechanism against MCA is unrelated to the original concept of T cell-mediated immune surveillance and that the increased spontaneous tumor incidence observed in some immune-deficient mice is likely to be explained by opportunistic infection and tumor-promoting chronic inflammation.
authors.affiliation: Max-Delbrück-Centrum for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blankenstein
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004249:DNA Damage; D005549:Foreign-Body Reaction / Q000276:immunology*; D007157:Immunologic Surveillance; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced* / Q000276:immunology; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D002273:Carcinogens; D008748:Methylcholanthrene; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor