T cell-mediated antitumor immune response eliminates skin tumors induced by mouse papillomavirus, MmuPV1

Abstract

Previous studies of naturally occurring mouse papillomavirus (PV) MmuPV1-induced tumors in B6.Cg-Foxn1 mice suggest that T cell deficiency is necessary and sufficient for the development of such tumors. To confirm this, MmuPV1-induced tumors were transplanted from T cell-deficient mice into immunocompetent congenic mice. Consequently, the tumors regressed and eventually disappeared. The elimination of MmuPV1-infected skin/tumors in immunocompetent mice was consistent with the induction of antitumor T cell immunity. This was confirmed by adoptive cell experiments using hyperimmune splenocytes collected from graft-recipient mice. In the present study, such splenocytes were injected into T cell-deficient mice infected with MmuPV1, and they eliminated both early-stage and fully formed tumors. We clearly show that anti-tumor T cell immunity activated during tumor regression in immunocompetent mice effectively eliminates tumors developing in T cell-deficient congenic mice. The results corroborate the notion that PV-induced tumors are strongly linked to the immune status of the host, and that PV antigens are major anti-tumor antigens. Successful anti-PV T cell responses should, therefore, lead to effective anti-tumor immune therapy in human PV-infected patients.

An Infection-Based Murine Model for Papillomavirus-Associated Head and Neck Cancer

“…Immune marker profiling has demonstrated that the oral cavity has a significantly higher concentration of T cell-related immune markers than the cervix, including higher levels of interleukin-2 (IL-2), an important T cell response marker that is often reduced during cervical HPV infection (63). Because T cell responses play crucial roles in MmuPV1 infection and associated disease (23,24,26,65), the oral cavity may be better protected against viral infection and associated tumorigenesis than the female reproductive tract because of the increased immunological surveillance in the former. This would support the hypothesis that MmuPV1 causes less severe disease in the tongue than in the cervix/vagina because it is more difficult for the virus to establish, maintain, and mediate pathogenesis in the oral cavity.…”

Rodent Papillomaviruses

“…Studies that involved intervention with immunosuppressants have been summarized in Table 4 . Recently, it has been reported that when MmuPV1-induced tumors arising in T-cell deficient mice were transplanted onto immunocompetent congenic mice, the tumors completely regressed [ 129 ]. Further, this elimination of MmuPV1-induced tumors was consistent with the induction of antitumor T cell immunity affirming the role of T-cell immunity in MmuPV1 infections.…”

The oncogenic pathways of papillomaviruses

“…To date, most of the current knowledge about the effects of PV infections on cellular transformation comes from immunological, oncological and virological studies in animal model systems 123,126 . In this context, many studies have evaluated the importance of cellular immune responses against these oncogenic DNA viruses to prevent malignant cell development 127 . The bovine model system has been used in many studies as a suitable model to investigate the oncogenic potential of this virus family and to elucidate the role of environmental co‐factors that accelerate and facilitate cellular transformation during PV infections 123 …”