Over 90% of breast cancer deaths are due to complications as a consequence of metastasis formation. Despite its devastating effects, metastatic disease is still poorly understood. Accumulating evidence indicates that cells and mediators of the immune system influence metastasis formation. In our lab, we use preclinical mouse models for metastatic breast cancer to dissect the impact of the immune system on the different steps of the metastatic cascade. Neutrophils make up a significant proportion of the inflammatory infiltrate in many tumors and their systemic accumulation in cancer patients has been associated with metastasis formation. Also in our recently developed spontaneous breast cancer metastasis mouse model that accurately mimics each step of the metastatic cascade in humans, metastasis formation is accompanied by pronounced systemic accumulation of neutrophils. Antibody-mediated depletion of neutrophils did not affect primary breast cancer outgrowth, but profoundly decreased spontaneous metastasis formation in lungs and lymph nodes. Using biological and genetic approaches, we have uncovered a novel mammary tumor-induced systemic communication network between gamma delta T cells and neutrophils that is critical for breast cancer metastasis. Our data indicate that targeting this novel cancer cell-initiated systemic inflammatory cascade represents a viable strategy to inhibit metastatic disease.
Citation Format: Seth B. Coffelt, Kelly Kersten, Max Wellenstein, Chris W. Doornebal, Camilla Salvagno, Kim Vrijland, Cheei-Sing Hau, Jos Jonkers, Karin E. de Visser. Cancer-associated systemic inflammation facilitates breast cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA04.
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