Co-targeting angiogenesis and immunosuppressive cell networks to improve anti-cancer therapy
Session type: Symposia
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.
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