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Patients with pancreatic cancer (PC) often suffer from refractory ascites associated with peritoneal metastasis. This severely impairs activities of daily living and leads to an unfavorable prognosis. Cell-free and concentrated ascites reinfusion therapy (CART) has attracted attention as a promising therapy for relieving the symptoms of malignant ascites. Accumulating evidence suggests that malignant ascites contains a variety of soluble factors, such as cytokines, that can be beneficial or detrimental in the prognosis of patients with refractory ascites. However, the expression profiles of these cytokines in the ascites before and after CART remain unknown. In this study, we used a comprehensive cytokine array to measure the expression levels of 102 cytokines in ascites derived from patients with PC before and after CART. The assay results revealed that the concentrations of several cytokines exacerbating tumor angiogenesis and tumor-suppressive interferon-gamma (IFN-γ) and interleukin-12 (IL-12) were higher in ascites after CART than before CART. Interestingly, growth of KP-2 human PC cells following exposure to ascites after CART decreased considerably compared to that before CART. Concomitant treatment of neutralizing antibodies against IFN-γ or IL-12 with ascites after CART restored the growth of KP-2 cells to the control level. These findings indicate that IFN-γ and IL-12 in ascites after CART may contribute to the inhibited growth of PC cells, highlighting their potential as biomarkers for assessing the clinical efficacy of CART procedures in patients with PC.
Kobori et al. (2022) studied this question.