Claudin-Low Breast Cancer Inflammatory Signatures Support Polarization of M1-Like Macrophages with Protumoral Activity
Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
Laboratorio de Biotecnología y Bioinformática Genómica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
Laboratorio Nacional de Microscopía Avanzada, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
Author to whom correspondence should be addressed.
Academic Editors: Georgios Giamas and Teresa Gagliano
Received: 22 March 2021 / Revised: 28 April 2021 / Accepted: 28 April 2021 / Published: 7 May 2021
Triple-negative breast cancer (BRCA) cells overexpress the cytokines GM-CSF, G-CSF, MCP-1, and RANTES. We have previously reported that monocytes in 3-D co-culture with BRCA cells generate M1-like macrophages with the ability to induce aggressive features in luminal BRCA cells. Here, we stimulated peripheral blood monocytes with the four cytokines, confirming their capacity to generate protumoral M1-like macrophages. We used the BRCA database to generate an M1-like macrophage gene expression signature related to these cytokines. We observed that the M1-like macrophage, Th1, and immunosuppressive signatures all coincide in claudin-low BRCA but also in mesenchymal carcinomas of colon (COAD) and bladder (BLCA), where they are associated with decreased overall survival in patients. Claudin-low is a tumor subtype with an adverse clinical outcome that remains poorly understood. This study indicates that M1 macrophages may be potential protumoral drivers in already established cancers, and may contribute to the aggressiveness and poor prognosis of claudin-low tumors. These results add to the knowledge of the claudin-low tumor microenvironment and could open a window to immunotherapy strategies to improve patient prognosis.