Abstract SP037: New insights to cancer-associated systemic inflammation

Abstract

Abstract The occurrence of distant metastases accounts for over 90% of breast cancer deaths. Despite these devastating effects, metastatic disease is poorly understood and incurable. Clearly, there is an urgent need for novel therapeutic strategies that prevent and/or cure metastatic disease. For successful dissemination and metastasis, cancer cells must evade detection and destruction by the immune system and adapt to a foreign tissue environment. This process is enabled by factors secreted by the primary tumor that shape both the intratumoral microenvironment and the systemic immune landscape. By manipulating systemic immune responses and creating conditions of chronic inflammation, tumors can have a long-distance reach and transform distant tissues that are intrinsically hostile to metastatic colonization into niches that are more hospitable for metastatic lesions to grow out. Key feature of this systemic process - often referred to as pre-metastatic niche formation- is the mobilization and polarization of (immature) myeloid immune cells from the bone marrow to the circulation, tumor and distant organs. We and others have used preclinical tumor models to demonstrate that these tumor-mobilized myeloid cells, including neutrophils and macrophages, contribute to a systemic immunosuppressive environment that inhibits anti-tumor immune responses and fosters metastasis formation. The pro-metastatic function of systemic inflammation is supported by clinical observations demonstrating that neutrophil accumulation in blood of cancer patients is strongly associated with poor survival and increased risk for metastasis. Targeting pro-metastatic inflammation represents an attractive strategy to prevent or treat metastatic disease. Importantly, the oncology field can benefit from compounds that have already been developed for the treatment of inflammatory diseases. In this Educational Session talk, I will discuss current insights into how tumors engage the immune system systemically, how systemic inflammation impacts disease progression and therapy response and how we can utilize these insights for the design of novel therapeutic opportunities. A great challenge in the field of immuno-oncology is the unexplained inter-patient heterogeneity in the intratumoral and systemic composition and functional state of the immune system. I will share some of our recent insights into how cancer cell-intrinsic mechanisms lie at the basis of this heterogeneity in the immune milieu of breast cancer, which may set the stage for personalized immune-intervention strategies. Citation Format: KE de Visser. New insights to cancer-associated systemic inflammation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP037.