UTMC effect on cancer cell apoptosis, proliferation, and vascular inflammation in wild type and CD39 knock out mice model of MC38 colon cancer

Purinergic signaling, governed by ATP and its conversion to adenosine, significantly impacts the immune responses within the tumor microenvironment. Ultrasound Targeted Microbubble Cavitation (UTMC) has been shown to enhance local ATP release in muscle and tumors. This study aimed to investigate the modulation of inflammatory responses following UTMC by ATP signaling within the tumor microenvironment. The expression of key markers related to vascular inflammation, apoptosis, and cell proliferation were examined 24h after UTMC treatment in wild-type (WT) and CD39 knockout (KO) mice. MC38 tumor cells were implanted in mice, and UTMC treatments (1MHz, 5000 cycles, 120 pulses total) were administered at different pressures (400 and 850 kPa). Immunohistochemistry and immunofluorescence analyses revealed that UTMC treatment led to increased apoptosis (CC3) and reduced cell proliferation (Ki67) in both WT and CD39KO mice, with the effect being more pronounced at p=850 kPa in CD39KO mice. Notably, UTMC treatment induced an increase in vascular inflammation markers (ICAM-1 and VCAM-1) in CD39KO mice, implying a potential role of ATP in mediating the immune responses triggered by UTMC. These findings highlight the intricate interplay between purinergic signaling, UTMC, and immune responses within the tumor microenvironment, offering insights into novel approaches for enhancing cancer immunotherapy.