Peritumoral macrophages recruit eosinophils to promote anti-tumor immune_x000D_responses in breast cancer

Breast tumors harbor dynamic tumor microenvironments, with multiple immune cell types often playing opposing roles during tumor progression and/or response to therapy.Tumor-associated macrophages (TAMs) are thought to promote mammary tumorigenesis, whereas the role of mammary tissue macrophages (MTMs) remains incompletely understood. High-dimensional immunostaining of murine mammary tumor progression revealed that MTMs were localized in the peritumoral stroma and associated with eosinophils, which were previously shown to facilitate anti-tumor T cell responses. The depletion of MTMs accelerated tumorigenesis in both spontaneous and orthotopically transplanted mammary tumor models. Upon induction of a productive anti-tumor response via the depletion of regulatory T cells (Tregs), MTMs assumed an alternatively activated state and expressed eotaxins, thereby attracting eosinophils to peritumoral regions. MTMs expressed the receptor for the alarmin IL-33, which induced both MTMactivation and eosinophil recruitment. Thus, MTMs sense IL-33 and recruit eosinophils to facilitate anti-tumor immunity – a mechanism that operates during tumor progression and can be enhanced during productive anti-tumor responses. Overall design: Two WT mice and two FoxP3-DTR mice were given a two-week DT regimen (500ng/100ul intraperitoneal on days 0, 1, 3, 8, and 14) and tumors were harvested and leukocytes isolated by FACS for CITE-seq.