Tumor-educated Tregs drive organ-specific metastasis in breast cancer by impairing NK cells in the lymph node niche

Breast cancer is accompanied by systemic immunosuppression, which facilitates metastasis formation, but how this shapes organotropism of metastasis is poorly understood. Here, we investigate the impact of mammary tumorigenesis on regulatory T cells (Tregs) in distant organs and how this affects multi-organ metastatic disease. Using a preclinical mouse mammary tumor model that recapitulates human metastatic breast cancer, we observe systemic accumulation of activated, highly immunosuppressive Tregs during primary tumor growth. Tumor-educated Tregs show tissue-specific transcriptional rewiring in response to mammary tumorigenesis. This has functional consequences for organotropism of metastasis, as Treg depletion reduces metastasis to tumor-draining lymph nodes, but not to lungs. Mechanistically, we find that Tregs control natural killer (NK) cell activation in lymph nodes, thereby facilitating lymph node metastasis. In line, an increased Treg/NK cell ratio is observed in sentinel lymph nodes of breast cancer patients compared with healthy controls. This study highlights that immune regulation of metastatic disease is highly organ dependent

Proposal for hadron production measurements using the NA49 detector for use in long-baseline and atmospheric neutrino flux calculations

O CIES Football Observatory é um site especializado na análise estatística do futebol. Foi fundado em 2005, por Raffaele Poli e Loïc Ravenel, aos quais se juntou Roger Besson, e é apoiado e enquadrado pelo Centre International d’Étude du Sport (Suíça). O prestígio deste Observatório reflete­-se nas inúmeras solicitações feitas por entidades como a Fédération Internationale de Football Association (FIFA), a Union of European Football Associations (UEFA), ou o Comité Olímpico Internacional. O t..