Poster Presentation 37th Lorne Cancer Conference 2025

Characterization of the immune microenvironment in pancreatic cancer following SARS-CoV-2 infection (#141)

Ka Yee Fung 1 2 , Trinity Peachey 1 2 , Suya Shen 1 2 , Aisling Ross 1 3 , Lauren Whelan 1 2 , Kate Sutherland 1 2 , Andreas Stresser 1 2 , Marcel Doerflinger 1 2 , Gemma Kelly 1 2 , Tracy Putoczki 1 2
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, parkville, Victoria, Australia
  3. School of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of Limerick, Limerick, Ireland

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal of all solid malignancies, with most patients succumbing to the disease within 6 months of diagnosis and only ~12% of patients surviving beyond 5 years. PDAC onset, progression and treatment response is associated with aberrant inflammation. For example, patients with chronic pancreatitis [1] or type II diabetes [2] have an increased risk of PDAC. Understanding the triggers and impact of inflammation could improve early detection, screening of those at risk of PDAC, and treatment options.

Many viruses can trigger inflammation. Emerging evidence has shown that SARS-CoV-2, a virus that caused the COVID-19 pandemic, can affect multiple organs. In particular, there is a strong correlation between severity of SARS-CoV-2 infection and pancreatic injury and inflammation [3, 4]. However, the mechanism underlying how SARS-CoV-2 infection leads to pancreatic impairment and how this may influence the development of PDAC has not been explored yet.

We hypothesised that SARS-CoV-2 infection would lead to inflammation of the pancreas, resulting in a pro-tumorigenic microenvironment. To this end, we infected a cohort of PDAC predisposed Pdx-1-Cre; LSL-KrasG12D/+ (KC) mice with a mouse adapted SARS-CoV-2 virus strain [5] that recapitulates key features of human COVID-19 disease. Immune cells within the pancreas microenvironment were quantified by flow cytometry and histopathology of pancreas tissue characterised.

Compared to uninfected littermate KC controls, we observed increased immune infiltration within the pancreas of SARS-CoV-2 infected mice, with the most striking changes including myeloid cell populations. We also observed an increase in the presence of inflammatory fibroblasts, which are a major source of pro-tumorigenic cytokines and linked to poor survival in PDAC. 

We have shown that the pancreas becomes inflamed following SARS-CoV-2 infection in mice, consistent with emerging epidemiological studies. We have further shown, using the KC model, that SARS-CoV-2 infection leads to changes in the microenvironment and we are now investigating whether these changes will alter the progression of pancreatic cancer. 

  1. 1. Kim, H.S., et al., Incidence and risk of pancreatic cancer in patients with chronic pancreatitis: defining the optimal subgroup for surveillance. Sci Rep, 2023. 13(1): p. 106.
  2. 2. Amri, F., et al., Association between pancreatic cancer and diabetes: insights from a retrospective cohort study. BMC Cancer, 2023. 23(1): p. 856.
  3. 3. Deng, W., et al., Infection with SARS-CoV-2 can cause pancreatic impairment. Signal Transduct Target Ther, 2024. 9(1): p. 98.
  4. 4. Wang, F., et al., Pancreatic Injury Patterns in Patients With Coronavirus Disease 19 Pneumonia. Gastroenterology, 2020. 159(1): p. 367-370.
  5. 5. Bader, S.M., et al., SARS-CoV-2 mouse adaptation selects virulence mutations that cause TNF-driven age-dependent severe disease with human correlates. Proc Natl Acad Sci U S A, 2023. 120(32): p. e2301689120.