In this week’s VJOncology podcast, we are joined by Philippe Spiess of Moffitt Cancer Center, Tampa, FL, to explore the role of tumor acidity in cancer progression and immune evasion. Dr Spiess discusses how the acidic tumor microenvironment suppresses T-cell function, the potential of pH modulation to enhance antitumor immunity and improve responses to immunotherapy, and preclinical findings on tumor growth and survival. He also outlines an upcoming first-in-human trial investigating transdermal delivery of a therapy designed to modulate tumor pH, including its rationale, key safety and efficacy biomarkers, and potential role in combination with existing immunotherapies.