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Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

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Timaxian, Colin | Vogel, Christoph, F A | Orcel, Charlotte | Vetter, Diana | Durochat, Camille | Chinal, Clarisse | Nguyen, Phuong | Aknin, Marie-Laure | Mercier-Nomé, Françoise | Martin, Davy | Raymond-Letron, Isabelle | Van, Thi-Nhu-Ngoc | Diermeier, Sarah, D | Godefroy, Anastasia | Gary-Bobo, Magali | Molina, Franck | Balabanian, Karl | Lazennec, Gwendal

Edité par CCSD ; MDPI -

International audience. Chemokines present in the tumor microenvironment are essential for the control of tumor progression. We show here that several ligands of the chemokine receptor Cxcr2 were up-regulated in the PyMT (polyoma middle T oncogene) model of breast cancer. Interestingly, the knock-down of Cxcr2 in PyMT animals led to an increased growth of the primary tumor and lung metastasis. The analysis of tumor content of PyMT-Cxcr2−/− animals highlighted an increased infiltration of tumor associated neutrophils (TANs), mirrored by a decreased recruitment of tumor associated macrophages (TAMs) compared to PyMT animals. Analysis of PyMT-Cxcr2−/− TANs revealed that they lost their killing ability compared to PyMT-Cxcr2+/+ TANs. The transcriptomic analysis of PyMT-Cxcr2−/− TANs showed that they had a more pronounced pro-tumor TAN2 profile compared to PyMT TANs. In particular, PyMT-Cxcr2−/− TANs displayed an up-regulation of the pathways involved in reactive oxygen species (ROS) production and angiogenesis and factors favoring metastasis, but reduced apoptosis. In summary, our data reveal that a lack of Cxcr2 provides TANs with pro-tumor effects.

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