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

Our plain-English summary of Lactate dehydrogenase-elevating virus enhances natural killer cell-mediated immunosurveillance of mouse mesothelioma development, by M.F. Mandour, P.P. Soe, C. Uyttenhove, et al (Infectious Agents and Cancer, 2020).

The study

• Authors: M.F. Mandour, P.P. Soe, C. Uyttenhove, J. Van Snick, E. Marbaix, J.P. Coutelier
• Journal: Infectious Agents and Cancer
• Published: 2020;15:30
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 dehydrogenase-elevating 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.

© The Author(s) 2020.

In plain English

This was a laboratory experiment in mice testing whether infection with lactate dehydrogenase-elevating virus (LDV) affects early growth of AB1 mouse mesothelioma cells. BALB/c mice were given AB1 cells into the abdomen one day after mock or LDV infection. Uninfected mice developed tumours and most were dead 40 days after tumour inoculation, while a majority of LDV-infected mice were still alive after two months (p = 0.0011); the authors reported a similar protective effect in 5 independent experiments. Histology 21 days after inoculation showed tumour infiltration in the mesentery of five out of five uninfected animals but no tumour lesions in the LDV group. LDV added to cultures did not change AB1 cell replication. Depleting natural killer (NK) cells with anti-ASGM1 almost completely removed the protection (p = 0.0021), as did neutralising gamma-interferon (p = 0.036); NK cells from infected mice did not lyse AB1 cells more than control NK cells. Neutralising interleukin-12 reduced survival (p = 0.0337) and IFN-gamma production. Protection was lost when infection came after tumour implantation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal (mouse) experiment with in vitro assays
• Who was studied: Female BALB/c and T-cell-deficient BALB/cAnNRj-Foxn1 nu/nu mice, 7-10 weeks old, in groups of 5 to 8, plus cultured AB1 mesothelioma, P815 mastocytoma and Yac-1 lymphoma cell lines; laboratory in Brussels, Belgium
• Exposure: Intraperitoneal infection with approximately 2 x 10^7 ID50 of lactate dehydrogenase-elevating virus (Riley strain), given one day before, one week after or two weeks after intraperitoneal injection of 0.5-1 x 10^6 AB1 mesothelioma cells; some mice also received anti-ASGM1, anti-IFN-gamma or anti-IL-12 antibodies
• Main results:
  • Uninfected mice mostly died by 40 days after AB1 inoculation, whereas most LDV-infected mice were alive after two months (p = 0.0011)
  • The protective effect was reproduced in 5 independent experiments
  • Histology at 21 days: mesenteric tumour infiltration in five of five uninfected mice (nodules in one), none in LDV-infected mice
  • LDV infection given one or two weeks after tumour cell administration gave no protection
  • LDV added to AB1 cultures did not alter cell growth (e.g. at day 7, 11.7 ± 2.22 x 10^5 cells without LDV vs 10.8 ± 1.36 x 10^5 with LDV)
  • NK cell depletion with anti-ASGM1 antibody nearly abolished the LDV protective effect (p = 0.0021)
  • In T-cell-deficient nu/nu mice, LDV infection still delayed death by about ten days (p = 0.0008)
  • NK cells from LDV-infected mice did not kill AB1 cells better than NK cells from control mice, although killing of Yac-1 target cells was enhanced
  • Neutralising gamma-interferon suppressed the LDV-induced protection (p = 0.036)
  • 0.9 U/ml gamma-interferon strongly reduced AB1 cell proliferation in culture but had no effect on P815 cells
  • Anti-IL-12 antibody in LDV-infected mice decreased survival (p = 0.0337) and lowered serum IFN-gamma (p = 0.0317) and IFN-gamma-producing NK cells (p = 0.0251)
• The authors' conclusion: The authors concluded that their results extend, in an experimental model of solid tumour, evidence that viral infections can enhance cancer immunosurveillance, through activation of NK cells and enhanced production of gamma-interferon
• Limitations the authors state:
  • The authors noted that cytokines other than IL-12 might also participate in the protective effect

Topics

Medical terms in this study, explained in our Lexicon: Lactate Dehydrogenase (LDH), Mesothelioma.

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