Therapeutic targeting of macrophages improves chemotherapy response and elicits neutrophil-dependent therapy resistance

Macrophages and neutrophils are almost invariably the most abundant intratumoral immune cells, and recent studies have revealed a sinister role for these cells in limiting chemotherapy efficacy. However, how these tumor-educated myeloid cells influence chemotherapy response is incompletely understood. Targeting tumor-associated macrophages by CSF-1 receptor (CSF-1R) blockade in a pre-clinical transgenic mouse model for breast cancer improved the anti-cancer efficacy of cisplatin. Importantly, our findings reveal that macrophage blockade in combination with cisplatin treatment evokes a compensatory neutrophil response limiting the therapeutic synergy of this therapy combination. Here we characterize neutrophils and macrophages gene expression profile from the tumor of mice treated with anti-CSF-1R, Control antibody, Cisplatin/anti-CSF-1R or cisplatin/control ab. Overall design: Intervention studies combining anti-CSF1R and chemotherapy in a transgenic mouse model for breast cancer.

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Salvagno C, Ciampricotti M, Tuit S, Hau CS, van Weverwijk A, Coffelt SB, Kersten K, Vrijland K, Kos K, Ulas T, Song JY, Ooi CH, Rüttinger D, Cassier PA, Jonkers J, Schultze JL, Ries CH, de Visser KE