Immune cell modulation of pulsed focused ultrasound in murine melanoma and breast cancer models

Authors

• P Chandran
• G Cohen
• R Lorsung
• O Aydin
• SR Burks
• JA Frank

Abstract

The present study showed the effect of pulsed focused ultrasound (pFUS) on tumor microenvironment (TME) immune cell profiles in spleen (Sp), lymph nodes (LN), and tumors at various peak negative pressures (PNP). Murine B16 melanoma and 4T1 mammary carcinoma cells were subcutaneously implanted into C57BL/6J and BALB/c mice (n=5/PNP), respectively. Ultrasound-guided pFUS at 1 MHz was administered to 5 mm tumors at PNP of 0, 2, 4, 6, 8 MPa. At days 1, 3, and 5 post-sonication, Sp, LN and tumors were harvested, fixed and processed for flow cytometry (FACS) analysis. FACS revealed 6MPa PNP drastically altered the immune cell profiles in B16 and 4T1 Sp, LN and tumors. B16 mice at days 1, 3 and 5 post-sonication revealed a 3-4 fold increase in Tcyt, Th, NK and M1 macrophage activity in tumor, which peaked at day 3, and decreased by day 5, compared to control tumors. At day 5, a shift of cell populations toward the LN, with increased Treg, Tcyt, NK, F4/80, M1 and M2 activity was observed. 4T1 mice showed high levels of Tcyt in Sp on day 1, and NK cells on day 3 in LN. Interestingly, these cell populations decreased in Sp and LN by day 5, with 3-4 fold increase in 4T1 tumors, along with increasing macrophage and DC activity. These results suggest that pFUS altered the TME by inducing anti-tumor responses by activating both innate and adaptive immunity, representing a shift from anti-inflammatory, immunosuppressive TME towards a pro-inflammatory and anti-tumor TME.

Scientific Focus Area: Immunology

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