Abstract IA15: Vascular reprogramming for enhancing cancer immunotherapy

Immune checkpoint blockade can reinvigorate the tumor-antagonizing functions of T cells and be potentially curative, but the majority of the tumors are either refractory or become resistant to the treatment. Among various parameters, the lack of pre-existing T-cell infiltrates may determine tumor refractoriness to immune checkpoint blockade and other cancer immunotherapies. Increasing data indicate that angiogenic blood vessels can limit the infiltration and functionality of T cells in tumors. For example, high intratumoral VEGFA levels make the tumor blood vessels dysfunctional and poorly permissive to T-cell extravasation, in part through the downregulation of T-cell adhesion molecules on the vascular endothelium. Besides VEGFA, angiopoietin-2 (ANGPT2) also induces abnormal tumor angiogenesis. Accordingly, combined blockade of VEGFA and ANGPT2 reprograms the tumor blood vessels to a form that is conducive to improved T-cell activation and trafficking and enhances tumor response to both immune checkpoint blockade (anti-PD-1) and agonistic CD40 antibodies in several genetically defined mouse cancer models. In my lecture I will discuss the applications, prospects, and current limitations of antiangiogenic immunotherapies.

Citation Format: Michele De Palma. Vascular reprogramming for enhancing cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr IA15.