Peritumoral macrophages recruit eosinophils to promote antitumor immune responses in breast cancer

• 成果类型: Article
• 署名作者: Saglimbeni, Joseph; Esteva, Eduardo; Canales, Josue; Perez, Oriana A.; Eichinger, Anna; Huntley, William; Khanna, Kamal M.; Dolgalev, Igor; Klar, Natalie; Adams, Sylvia; Reizis, Boris
• 署名单位: New York University; New York University; New York University; University of Munich; New York University; New York University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8914
• DOI: 10.1073/pnas.2504645122
• 发表日期: 2025-09-23
• 关键词: tumor-infiltrating lymphocytes; expression; cells; eotaxin; pembrolizumab; interleukin-5; chemotherapy; oncogene; MODEL

摘要

Breast tumors harbor dynamic microenvironments, with multiple immune cell types playing opposing roles during tumor progression and/or response to therapy. Tumor- associated macrophages 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 antitumor T cell responses. The depletion of MTMs accelerated tumorigenesis in both spontaneous and orthotopically transplanted mammary tumor models. Upon induction of a productive antitumor response via the depletion of regulatory T cells, 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 MTM activation and eosinophil recruitment. These results suggest that MTMs can sense IL- 33 and recruit eosinophils to facilitate antitumor immunity, a mechanism that may operate during tumor progression and be further enhanced during productive antitumor responses.