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Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance

Item Type:Review
Title:Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance
Creators Name:Blankenstein, T. and Qin, Z.
Abstract:Interferon-{gamma}-receptor (IFN{gamma}R)-deficient mice are more susceptible to tumor induction by methylcholanthrene (MCA) in comparison to control littermates. The cellular source of IFN{gamma}γ 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 IFN{gamma}R-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.
Keywords:Carcinogens, DNA Damage, Foreign-Body Reaction, Immunologic Surveillance, Interferon Receptors, Methylcholanthrene, Neoplasms, Animals, Mice
Source:Advances in Cancer Research
Publisher:Elsevier / Academic Press
Page Range:179-207
Official Publication:https://doi.org/10.1016/S0065-230X(03)90006-6
PubMed:View item in PubMed

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