Repeated COVID-19 Vaccination as a Poor Prognostic Factor in Pancreatic Cancer: A Retrospective, Single-Center Cohort Study

<b>Background/Objectives</b>: The COVID-19 vaccine is a significant technological advancement with widespread global use. However, its effect on cancer immunity, particularly with repeated vaccinations, remains unclear. We aimed to investigate the relationship between repeated vaccinations and pancreatic cancer (PC) prognosis. Additionally, we examined serum IgG4 levels, known to be an immune suppressor which increases with repeated vaccinations. <b>Methods</b>: We retrospectively examined the effect of vaccination on survival in 272 PC patients diagnosed at our hospital from January 2018 to November 2023 and analyzed prognostic factors, including IgG4 levels in 96 PC patients. Immunohistochemistry for Foxp3 in the tumor tissue was performed, and the serum IgG4 level was measured. Serum samples from 79 patients with benign and malignant diseases, including PC, were collected between September and November 2023, and the spike-specific IgG4 level was determined using an enzyme-linked immunosorbent assay. <b>Results</b>: The overall survival (OS) of PC patients was shortened in those vaccinated three times or more, and the total serum IgG4 levels increased with the number of vaccinations. Of note, OS was significantly shorter in the high IgG4 group, and Foxp3-positive cells in the tumor tissues were increased. Repeated vaccinations increased the spike-specific IgG4 levels, and a positive correlation was observed between spike-specific IgG4 and the total IgG4. <b>Conclusions</b>: These findings highlight repeated vaccination as a poor prognostic factor in PC patients and suggest that IgG4 is induced by repeated vaccination and may be associated with a poor prognosis in these patients.