Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade
Martina Schmittnaegel(École Polytechnique Fédérale de Lausanne), Nicolò Rigamonti(École Polytechnique Fédérale de Lausanne), Ece Kadioglu(École Polytechnique Fédérale de Lausanne), Antonino Cassará(École Polytechnique Fédérale de Lausanne), Céline Wyser Rmili(École Polytechnique Fédérale de Lausanne), Anna Kiialainen(Roche (Switzerland)), Yvonne Kienast(Roche Pharma AG (Germany)), H.P. Mueller(Roche Pharma AG (Germany)), Chia-Huey Ooi(Roche (Switzerland)), Damya Laoui(École Polytechnique Fédérale de Lausanne), Michele De Palma(École Polytechnique Fédérale de Lausanne)
Cited by 575Open Access
Abstract
cytotoxic T lymphocytes (CTLs). Whereas the antitumoral activity of A2V was, at least partly, CTL-dependent, perivascular T cells concurrently up-regulated the expression of the immune checkpoint ligand programmed cell death ligand 1 (PD-L1) in tumor endothelial cells. IFNγ neutralization blunted this adaptive response, and PD-1 blockade improved tumor control by A2V in different cancer models. These findings position immune cells as key effectors of antiangiogenic therapy and support the rationale for cotargeting angiogenesis and immune checkpoints in cancer therapy.
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