The findings suggest ERα-active macrophages create a protective niche for bone metastases, and targeting ERα signaling in macrophages could enhance immune clearance of metastatic tumors across genders and cancer types.

In bone metastases, macrophages with active estrogen receptor alpha (ERα) signaling were found—a phenomenon not seen in normal bone or primary tumors of other tissues—detected in human samples from breast, lung, and kidney cancers, including male patients.

A surprising result is that macrophages surrounding bone metastases activate ERα, a signaling pathway not typically studied in immune cells, contributing to an immunosuppressive environment.

A new method, SAMENT, identifies the cellular makeup of metastatic niches across multiple organs.

The research appears in Cell, with full contributor and funding details available in the linked article.

The study, titled Unbiased niche labeling maps immune-excluded niche in bone metastasis, was published in Cell in 2026 (DOI: 10.1016/j.cell.2026.04.009).

In mouse models, fulvestrant treatment similarly enabled T cell infiltration into bone metastases and tumor killing, supporting potential combination therapies across cancer types.

Across cancer models, metastatic niches show high macrophage presence and reduced T cell activity, highlighting macrophages’ central role in immunosuppression within these environments.

Baylor College of Medicine researchers developed SAMENT (Sortase A–Based Microenvironment Niche Tagging) to map the cellular makeup of metastatic tumor niches across multiple organs, revealing shared features such as abundant macrophages and scarce T cells.

SAMENT labels normal cells that come into direct contact with disseminating cancer cells, enabling precise mapping of metastatic niches in bone, lung, liver, and brain.

Pharmacological degradation of estrogen receptors with fulvestrant enables T cells to infiltrate bone metastases and kill tumor cells, suggesting potential for combination therapies.

Blocking ERα signaling with fulvestrant, an FDA-approved estrogen receptor degrader, facilitates T cell infiltration and tumor cell killing in bone metastases, pointing to combination strategies.