Investigating The Potential of Focused Ultrasound Mediated Hyperthermia on Improving the Efficacy of Anti PD-L1 Blockade in Brain Cancer
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Sridhar, Shwetha
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Abstract
Receptor-ligand binding between the immune cells and the cancer cells are known to aid the tumors in immunosuppression and evasion. Blocking this interaction through checkpoint inhibitors has shown great promise in treating various types of cancer. Despite its success in peripheral tumors, there has been very poor efficacy in brain tumors such as glioblastoma. This poor efficacy is partially attributed to the presence of tumor hypoxia, an important hallmark of cancer, which is known to suppress the impact of immune checkpoint inhibitors. Mild temperature hyperthermia is known to enhance tumor oxygenation by improving blood perfusion and tumor vascularization. Here, we hypothesized Magnetic resonance guided Focused ultrasound (MRgFUS) mediated hyperthermia can alleviate tumor hypoxia and improve the effectiveness of PD-L1 blockade in glioblastoma. Our results show that closed loop MRgFUS mediated mild temperature hyperthermia (~41.5 ̊C) led to a significant reduction (P<0.05) of hypoxic region in GL261 tumor compared to control non-heated tumors. Moreover the combination therapy of FUS mediated hyperthermia and PD-L1 blockade showed a trend in the survival improvement of GBM tumor bearing mice. Together, our findings demonstrate the ability of MRgFUS mediated mild temperature hyperthermia to modulate the tumor microenvironment and potentially improve the efficacy of immunotherapy in brain cancer.
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2024-04-30
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