TY - JOUR
T1 - Claudin‐low breast cancer inflammatory signatures support polarization of m1‐like macrophages with protumoral activity
AU - Suárez‐arriaga, Mayra Cecilia
AU - Méndez‐tenorio, Alfonso
AU - Pérez‐koldenkova, Vadim
AU - Fuentes‐pananá, Ezequiel M.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - We previously reported that triple‐negative breast cancer (BRCA) cells overexpress the cytokines GM‐CSF, G‐CSF, MCP‐1, and RANTES, and when monocytes were 3‐D co‐cultured with them, M1‐like macrophages were generated with the ability to induce aggressive features in luminal BRCA cell lines. These include upregulation of mesenchymal and stemness markers and invasion. In this study, we stimulated peripheral blood monocytes with the four cytokines and confirmed their capacity to generate protumoral M1‐like macrophages. Using the METABRIC BRCA database, we observed that GM‐CSF, MCP‐1, and RANTES are associated with tri-ple‐negative BRCA and reduced overall survival, particularly in patients under 55 years of age. We propose an extended M1‐like macrophage proinflammatory signature connected with these three cytokines. We found that the extended M1‐like macrophage signature coexists with mono-cyte/macrophage, Th1 immune response, and immunosuppressive signatures, and all are enriched in claudin‐low BRCA samples, and correlate with reduced patient overall survival. Furthermore, we observed that all these signatures are also present in mesenchymal carcinomas of the colon (COAD) and bladder (BLCA). The claudin‐low tumor subtype has an adverse clinical outcome and remains poorly understood. This study places M1 macrophages as potential protumoral drivers in already established cancers, and as potential contributors to claudin‐low aggressiveness and poor prognosis.
AB - We previously reported that triple‐negative breast cancer (BRCA) cells overexpress the cytokines GM‐CSF, G‐CSF, MCP‐1, and RANTES, and when monocytes were 3‐D co‐cultured with them, M1‐like macrophages were generated with the ability to induce aggressive features in luminal BRCA cell lines. These include upregulation of mesenchymal and stemness markers and invasion. In this study, we stimulated peripheral blood monocytes with the four cytokines and confirmed their capacity to generate protumoral M1‐like macrophages. Using the METABRIC BRCA database, we observed that GM‐CSF, MCP‐1, and RANTES are associated with tri-ple‐negative BRCA and reduced overall survival, particularly in patients under 55 years of age. We propose an extended M1‐like macrophage proinflammatory signature connected with these three cytokines. We found that the extended M1‐like macrophage signature coexists with mono-cyte/macrophage, Th1 immune response, and immunosuppressive signatures, and all are enriched in claudin‐low BRCA samples, and correlate with reduced patient overall survival. Furthermore, we observed that all these signatures are also present in mesenchymal carcinomas of the colon (COAD) and bladder (BLCA). The claudin‐low tumor subtype has an adverse clinical outcome and remains poorly understood. This study places M1 macrophages as potential protumoral drivers in already established cancers, and as potential contributors to claudin‐low aggressiveness and poor prognosis.
KW - Breast cancer
KW - Claudin‐low
KW - M1‐like macrophages
KW - Protumoral activity
KW - Tumor microen-vironment
UR - http://www.scopus.com/inward/record.url?scp=85105374877&partnerID=8YFLogxK
U2 - 10.3390/cancers13092248
DO - 10.3390/cancers13092248
M3 - Artículo
C2 - 34067089
AN - SCOPUS:85105374877
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 9
M1 - 2248
ER -