Non-ablative focused ultrasound induces an adaptive immune response to suppress pancreatic cancer: a preclinical study

Purpose This study aimed to investigate whether, and by what mechanisms, focused ultrasound–mediated mechanical stimulation (MS) can induce anti-tumor immunity and elicit an abscopal effect in a pancreatic cancer model. Methods In study 1, animals bearing unilateral murine pancreatic tumors (Pan02) in the flank were divided into five groups according to the single or combined use of gemcitabine (Gem), thermal ablation, or MS. Study 2 was conducted in mice bearing bilateral flank tumors to evaluate abscopal effects. Tumor growth suppression, tissue damage, expression of tumor growth-inhibitory genes and cytokines, and anti-tumor cytotoxic T lymphocyte responses were analyzed. Results In study 1, the MS+Gem group exhibited significantly higher levels of interleukin-6, KC-GRO, and tumor necrosis factor-α; higher proportions of CD8+ cells and granzyme B (GrB); and lower Foxp3 expression than the other groups. A significantly higher ratio of CD8+ cells among tumor-infiltrating lymphocytes (TIL) was also observed in the MS+Gem group (P<0.005 at week 2). In study 2, significant growth suppression of the untreated contralateral tumor was observed in the MS+Gem group. Immune analysis of the untreated tumor showed significantly higher proportions of CD8+ cells and GrB, along with a lower proportion of Foxp3+ cells, in the MS+Gem group. The MS+Gem group also demonstrated a higher CD8+/TIL ratio in the untreated tumor. Conclusion MS+Gem effectively suppressed tumor growth, promoted apoptosis-related factors, and enhanced intratumoral infiltration of cytotoxic T cells in treated tumors. In addition, MS+Gem induced an abscopal effect in untreated tumors, suggesting its potential to mediate systemic anti-tumor immune responses in pancreatic cancer treatment.