Abstracts Division 2

46. Pneumococcal immunization against oxLDL decreases tumor burden in NASH-derived hepatocellular carcinoma

LM Stoffels1,2, AV Bitorina1, AJF Westheim2, J Verbeek3, T Hendrikx4, J Theys2, R Shiri-Sverdlov1

1 Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
2 Department of Precision Medicine, School for Oncology & Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, the Netherlands
3 Department of Gastroenterology & Hepatology, University Hospitals Leuven; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
4 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

Perturbed lipid metabolism, as observed in non-alcoholic steatohepatitis (NASH), has been linked to the development of hepatocellular carcinoma (HCC). In particular, increased production of oxidized low-density lipoprotein (oxLDL) has been associated with metabolic disturbances and inflammation. Previously, we have demonstrated that immunization with heat-inactivated pneumococci increased the production of anti-oxLDL antibodies, due to molecular mimicry with oxLDL, thereby leading to reduced hepatic inflammation in NASH. However, the effect of anti-oxLDL immunization on the occurrence and progression of NASH to HCC, is currently unexplored.

In this study, we used a non-alcoholic steatohepatitis (NASH) induced HCC mouse model, in which neonatal male mice were exposed to a low dose streptozotocin (STZ), followed by a high fat diet (HFD) after which all mice developed HCC. To test the effect of immunization against oxLDL on HCC occurrence and progression, mice (n=20) were split into 2 groups either receiving a subcutaneous injection with heat-inactivated Streptococcus pneumonia (108 CFU) or control-injection (0,9% NaCl). Plasma anti-oxLDL titers were measured and tumor growth rate and number of tumors were assessed through CT imaging. Additionally, apoptosis was quantified with TUNEL staining.

Immunization with heat-inactivated Streptococcus pneumonia resulted in increased plasma titers of anti-oxLDL IgM compared to control mice. Immunization reduced both the number of tumors and tumor growth rate compared to control injection. Hepatic TUNEL staining showed increased apoptosis in immunized versus control mice.

Immunization with heat-inactivated Streptococcus pneumonia could potentially be a viable strategy to inhibit progression of NASH-derived HCC.

NUTRIM | School of Nutrition and Translational Research in Metabolism
NUTRIM aims to contribute to health maintenance and personalised medicine by unraveling lifestyle and disease-induced derangements in metabolism and by developing targeted nutritional, exercise and drug interventions. This is facilitated by a state of the art research infrastructure and close interaction between scientists, clinicians, master and PhD students.