Transferable anticancer innate immunity in spontaneous regression/complete resistance mice

Abstract

Spontaneous regression͞complete resistance (SR͞CR) mice resist very high doses of cancer cells that are lethal to WT mice even at low doses. In this study, we show that this resistance is mediated by rapid infiltration of leukocytes, mostly of innate immunity, in both primary and repeated challenges. Formation of rosettes with infiltrating natural killer cells, neutrophils, and macrophages was required for the subsequent destruction of cancer cells through rapid cytolysis. Highly purified natural killer cells, macrophages, and neutrophils from the SR͞CR mice independently killed cancer cells in vitro. The independent killing activity by each subset of effector cells is consistent with the observation that the resistance was abolished by depleting total infiltrating leukocytes but not by depleting only one or two subsets of leukocytes. The resistance was completely transferable to WT recipient mice through SR͞CR splenocytes, bone marrow cells, or enriched peritoneal macrophages, either for prevention against subsequent cancer challenges or eradication of established malignancy at distant sites. cellular cancer immunity ͉ adoptive transfer ͉ cancer therapy ͉ macrophages ͉ leukocyte depletion

Toll-like receptors in cancer

“…TLRs are primary drivers of innate immunity, and there is increasing evidence that innate cells such as macrophages and neutrophils have potent antitumour effects. This has most recently been seen in a study by Hicks et al (2006), who have demonstrated that the basis for complete tumour resistance in the spontaneous regression/complete resistance mouse is due to innate cells whose antitumour effect can be adoptively transferred to recipient mice. Cancer researchers investigating antitumour immunity are colloquially referring to the Toll-like receptors in cancer LAJ O'Neill donor mouse as the 'wonder mouse' (J Obijeski, personal communication), and there is a strong likelihood that TLRs are involved in this process.…”

Clonally transmissible cancers in dogs and Tasmanian devils

“…A spontaneously arising sarcoma was found to be transmissible among a colony of Syrian hamsters (Brindley and Banfield, 1961;Cooper et al, 1964), and this cancer could even be experimentally transferred between individuals by mosquitoes (Banfield et al, 1965). A number of mouse cancer cell lines can be propagated by intraperitoneal injection through unrelated mouse strains (Carry et al, 1979;Hicks et al, 2006). Transmissible cancers with unknown etiology, some of which are transplantable, have been described in newts and fish (Champy and Champy, 1935;Lucke and Schlumberger, 1949).…”

Toll-like Receptor 5 Agonist Inhibition of Growth of A549 Lung Cancer Cells in Vivo in a Myd88 Dependent Manner

“…In the current study, the inhibition of MyD88 promoted the tumor progression. In the previous study, infiltrating inflammatory cells, such as neutrophils and macrophages, could destroy cancer cells by rapid cytolysis (Hicks et al, 2006). Furthermore, neutrophils also showed antituomor effects in several types of cancer models (Challacombe et al, 2006;Nozawa et al, 2006).…”