Anti-Csf-1R Therapy With Combined Immuno-Chemotherapy Coordinate an Adaptive Immune Response to Eliminate Macrophage Enriched Triple Negative Breast Cancers

Authors

Diego A Pedroza
Xueying Yuan
Fengshuo Liu
Hilda L Chan
Christina Zhang
William Bowie
Alex J Smith
Sebastian J Calderon
Nadia Lieu
Weiguo Wu
Paul Porter
Poonam Sarkar
Na Zhao
Constanze V Oehler
Ondrej Peller
M Waleed Gaber
Qian Zhu
Charles M Perou
Xiang H-F Zhang
Jeffrey M Rosen

Language

English

Publication Date

1-3-2026

Journal

Nature Communications

DOI

10.1038/s41467-025-67964-2

PMID

41484081

Abstract

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along with CTX disrupted the M-CSF/CSF-1R axis which upregulated IL-17, IL-5 and type II interferon resulting in elevated B- and T cell infiltration. Addition of an anti-PD-1 maintenance dose helped overcome de novo PD-L1 intra-tumoral heterogeneity (ITH) associated recurrence in lung and liver mTNBC.

Published Open-Access

yes

Recommended Citation

Pedroza, Diego A; Yuan, Xueying; Liu, Fengshuo; et al., "Anti-Csf-1R Therapy With Combined Immuno-Chemotherapy Coordinate an Adaptive Immune Response to Eliminate Macrophage Enriched Triple Negative Breast Cancers" (2026). Faculty, Staff and Students Publications. 4987.
https://digitalcommons.library.tmc.edu/baylor_docs/4987