Annually, approximately 500,000 new cases of pancreatic ductal adenocarcinoma (PDAC) are diagnosed worldwide, with the same number of patients dying from this debilitating disease. Treatment resistance in PDAC results from the general immune suppression aggravated by the dense tumor stroma, which acts as a physical barrier to far too many treatment agents. Numerous studies suggest that RFA can trigger tumor-specific immune stimulation along with the disruption of the dense tumor stroma. Despite the immune stimulatory effect of RFA seen after procedure, a long-lasting clinical outcome of this procedure is hard to achieve. We aimed to explore the dynamics of immunological parameters in patients with PDAC treated with repetitive (three rounds of) RFA. Peripheral blood samples were analyzed from patients with inoperable pancreatic cancer who received three RFA treatments in a row, and compared to age-matched healthy controls. Only repetitive, and not a sole, administration of RFA actuated the decrease in protumorigenic cytokines (TGF-β, IL-17) and protumorigenic CD4+CD39+ and naive CD45RA T cells. Our study provides the first evidence on immunomodulatory benefits of repetitive RFA in patients with inoperable pancreatic cancer. Despite the fact that there was no other treatment used in the RFA group we still cannot attribute these immunologic changes to RFA alone. Larger scale studies involving different treatment modalities and complex immune readouts would guarantee more certainty to the clinical advantages of repetitive RFA.
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