Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer
Menée in vitro et à l'aide de modèles murins de cancer mammaire, cette étude met en évidence un mécanisme par lequel les monocytes et les neutrophiles, induits par la tumeur primitive, préviennent le développement de métastases en éliminant les cellules tumorales disséminées
Metastatic breast cancer is a major clinical challenge, accounting for a discouraging 400,000 deaths per year worldwide. Novel therapeutic alternatives are urgently needed. Cancer immunotherapy has proven to be a promising treatment, improving the survival of patients with cancer; however, currently there are no immunotherapies available for advanced breast cancer. Importantly, current cancer immunotherapies primarily target T lymphocytes rather than myeloid cells, which are critical regulators of metastatic breast cancer. Novel cancer immunotherapies that directly regulate the function of various antitumoral myeloid subpopulations in breast cancer could have therapeutic potential and target metastatic breast cancer.Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic progression. The primary tumor systemically recruits IFNγ-producing immune effector monocytes to the lung. IFNγ up-regulates Tmem173/STING in neutrophils and enhances their killing capacity. The immune effector monocytes and tumoricidal neutrophils target disseminated tumor cells in the lungs, preventing metastatic outgrowth. Importantly, our findings could underlie the development of immunotherapeutic target molecules that augment the function of immune effector monocytes and neutrophils.