Lactate dehydrogenase-elevating virus enhances natural killer cell-mediated immunosurveillance of mouse mesothelioma development

Abstract

Background: Viral infections can reduce early cancer development through enhancement of cancer immunosurveillance. This study was performed to analyse this effect of viral infection in a mouse model of solid tumor. Methods: The experimental model used was the effect of BALB/c mouse infection by lactate dehydrogenaseelevating virus on AB1 mesothelioma cancer development. Results: Acute infection with lactate dehydrogenase-elevating virus strongly reduced in vivo early AB1 mesothelioma growth and death resulting from cancer development. This effect was not due to a direct cytolytic effect of the virus on AB1 cells, but to an in vivo activation of natural killer cells. Gamma-interferon production rather than cytotoxic activity against AB1 cells mediated this protective effect. This gamma-interferon production by natural killer cells was dependent on interleukin-12 production. Conclusions: Together with other reported effects of infectious agents on cancer development, this observation may support the hypothesis that enhancement of innate immunosurveillance against tumors may result from infection with common infectious agents through modulation of the host immune microenvironment.

Degenerative Myelopathy and Neuropathy in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) Mice Caused by Lactate Dehydrogenase–Elevating Virus (LDV)

“…16 In addition, LDV infection may affect successful engraftment, normal growth, biologic behavior, and response to therapy of implanted tumors. 17,18…”

“…16 In addition, LDV infection may affect successful engraftment, normal growth, biologic behavior, and response to therapy of implanted tumors. 17,18 In immunocompetent strains, infection with LDV can modify the host immune response. Immunomodulatory effects of LDV infection include nonspecific polyclonal activation of B cells, immunoglobulin secretion, acute lymphopenia, chronic lymphocytosis, and abnormal interferon and natural killer (NK) cell responses.…”

Inhibition of IL-12 heterodimers impairs TLR9-mediated prevention of early mouse plasmacytoma cell growth

“…Lactate dehydrogenase-elevating virus infection has been shown to protect against mesothelioma early growth through mechanisms similar to those involved in protection against plasmacytoma (11). To determine whether our observation of protection against early plasmacytoma growth after CpG-ODN stimulation could be extended to other tumors, we repeated therefore our experiments after administration of AB1 mesothelioma cells.…”

“…Such an effect of infections may explain a lower incidence of some cancers, including multiple myeloma (8) in developing countries when compared to industrialized countries. Cancer development has been shown to be prevented by previous infection with lactate dehydrogenaseelevating virus (LDV), a virus inducing lifelong viremia, (9) and Trypanosoma brucei (10) in experimental mouse models of myeloma and mesothelioma (11). This led to the proposal that a particular form of "hygiene hypothesis" might apply to cancer development.…”

Proceedings of the 2022 National Toxicology Program Satellite Symposium

“…Infection with LDV in immunocompromised mice used for tumor transplant studies can result in alteration in the efficiency of xenograftment causing transplant failure, and can alter the growth and progression of xenograft tumors in recipient mice. 53,54 Therefore, the presence of this virus in tumor transplant studies can significantly impact cancer studies in biomedical research. Therefore, it is clear that the effects of this virus are far more reaching and significant than merely transient elevation in serum LDH.…”