(510c) Reengineering the Tumor Microenvironment for Immunotherapy

Cancer cells promote the development of abnormal blood and lymphatic vessels through altered signaling and increased mechanical stress. This creates a hostile tumor microenvironment featuring hypoxia, acidity, and elevated interstitial fluid pressure. These abnormalities fuel disease progression, immunosuppression, and treatment resistance. Judicious use of antiangiogenesis agents that block the altered signaling can transiently ‘normalize’ tumor vessels. In parallel, because desmoplasia impairs vascular function by compressing vessels, normalizing the extracellular matrix also can improve vascular function. Here, I will present the progress made in understanding and applying the normalization concept to cancer and outline opportunities to improve the efficacy of emerging immunotherapies.