Researchers propose combining macrophage-targeted approaches with existing therapies to broaden cancer treatment effectiveness across melanoma and potentially other solid tumors.

CD169-positive macrophages, a skin macrophage subset, appear to suppress melanoma growth, with experiments showing larger tumors when these cells are removed.

The same CD169-positive macrophages surround melanomas and help constrain progression by consuming live cancer cells.

A study published in the Journal of Experimental Medicine on May 21, 2026, suggests macrophage involvement against melanoma could extend to other solid tumors and may help address tumors that resist T cell–focused therapies.

Using intravital two-photon microscopy in mice, researchers watched macrophages actively attack and engulf live melanoma cells in real time, with human tissue from Melanoma Institute Australia showing the same macrophage subset near tumor edges.

This is the first real-time observation of macrophages engulfing live melanoma cells, revealing an anti-tumor role for these immune cells.

A Garvan Institute team recorded the same phenomenon, confirming macrophages actively attacking and engulfing live melanoma cells in real time.

The work was funded by multiple Australian institutions and foundations, including NHMRC, Australian Cancer Research Foundation, and Melanoma Institute Australia, with the DOI 10.1084/jem.20252239.

Findings point to strategies that boost CD169-positive macrophages or enhance their ability to tag cancer cells for immune attack, potentially expanding immunotherapy beyond T cell–dependent approaches.

The study suggests macrophages can act independently of T and B cells and may serve as immune informants by presenting cancer-cell fragments to alert other immune players.

CD169-positive macrophages may function as immune informants by displaying cancer-cell fragments on their surface to attract T cells and boost anti-tumor immunity.

Removing CD169-positive macrophages led to larger tumors, underscoring their role in inhibiting melanoma growth.