A collaboration between researchers at Mass General Hospital and Brigham and Women’s led to fruitful findings for a transformative approach to Hepatocellular carcinoma (HCC). The team began with hopes to address the current limitations of immune checkpoint blockade (ICB). A new class of drugs that despite demonstrating the ability to enhance anti-tumor immunity, only elicit responses in a small fraction of patients. Through use of p53 targeted mRNA nanoparticles, researchers were able to restore p53 function in an immunosuppressed environment to potentiate ICB response in HCC murine models. Success was observed through effective reprogramming of the tumor microenvironment and suppression of tumor growth.