Co-targeting angiogenesis and immunosuppressive cell networks to improve anti-cancer therapy


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Michele De Palma1,
The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland (1)

Abstract

We have recently shown that angiopoietin-2 (ANG2/ANGPT2), a proangiogenic factor that promotes endothelial-cell survival and growth by activating the TIE2 receptor, may limit tumour sensitivity to vascular-endothelial growth factor (VEGFA)-targeted therapies. Indeed, combined ANG2/VEGF signalling blockade suppresses tumour angiogenesis and progression in tumours that adaptively up-regulate ANG2 in response to VEGFA blockade (Rigamonti et al., Cell Reports 2014). Although these findings support the clinical rationale for co-targeting ANG2 and VEGFA in tumours that develop resistance to VEGFA inhibition, tumour-associated macrophages (TAMs) represent an important source of pro-angiogenic and immunosuppressive signals that can contribute to abate the efficacy of anti-angiogenic therapy. To address this issue, we are currently developing combination treatments that involve co-targeting angiogenesis and immunosuppressive TAMs, as well as re-stimulating T cells, primarily in mouse models of breast cancer. The results of these studies will be presented at the Conference.

Full authorship

Nicolo' Rigamonti1, Celine Rmili-Wyser1, Hans-Joachim Mueller2, Carola Ries2, and Michele De Palma1

1The Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland

2Roche Diagnostics GmbH, Penzberg, Germany

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