Data from Anti-VEGF Treatment Enhances CD8⁺ T-cell Antitumor Activity by Amplifying Hypoxia

• DOI: 10.1158/2326-6066.c.6550410.v1
• Publication Date: 2023-04-04T19:39:13Z
• Authors: Patricia E. de Al...; Judy Mak; Genevive Hernandez; Rajiv Jesudason; Aurelie Herault; Vincent Javinal; Jovencio Borneo; Jeong M. Kim; Kevin B. Walsh
• Keywords: Tumor Hypoxia

<div>Abstract<p>Antiangiogenic therapies that target the VEGF pathway have been used clinically to combat cancer for over a decade. Beyond having direct impact on blood vessel development and tumor perfusion, accumulating evidence indicates these agents also affect antitumor immune responses. Numerous clinical trials combining antiangiogenic drugs with immunotherapies treatment of are ongoing, but mechanistic understanding how disruption angiogenesis may immunity is not fully discerned. Here, we reveal blockade VEGF-A mAb augments activation CD8<sup>+</sup> T cells within tumors potentiates their capacity produce cytokines. We demonstrate this phenomenon relies VEGFR2 signaling in microenvironment does directly. Instead, augmented functional stems from increased hypoxia initiates hypoxia-inducible factor-1α program directly enhances cytokine production. Finally, combinatorial administration anti-VEGF an immunotherapeutic antibody, anti-OX40, improved activity single-agent treatments. Our findings illustrate T-cell effector function provides rationale treatment.</p></div>