JERUSALEM — Inside every tumor, macrophages circulate doing what immune cells are designed to do: clearing away dead and dying cancer cells, disposing of cellular waste. Researchers at Tel Aviv University now say that process, long considered a basic function of immune maintenance, is precisely how tumors recruit those immune cells as allies.
The finding, published in Science Immunology, documents how efferocytosis, the routine by which macrophages engulf and dispose of dead cells, transforms the macrophages themselves. After consuming dead cancer cells, these immune cells activate a new set of genes, shifting from defenders of the body into growth promoters that supply tumors with oxygen and block the signals that would otherwise trigger an anti-cancer immune response.
The study was led by Dr. Merav Cohen of Tel Aviv University’s Gray Faculty of Medical and Health Sciences, with doctoral students Roi Balaban and Ori Moskowitz contributing to the research. The paper, titled “Efferocytosis induces proangiogenic function and chromatin remodeling in tumor-associated macrophages,” describes a mechanism the immune system has no obvious way to avoid.
To observe the transformation in real time, the team developed a technology called Effero-seq. Previous methods for studying macrophage behavior provided snapshots of gene activity; Effero-seq enables continuous monitoring of how a macrophage’s gene expression changes after it engulfs dead cells. That tracking capacity was what made the reprogramming visible. Earlier studies of tumor-associated macrophages had established that they often promote tumor growth rather than suppress it, but the connection between efferocytosis and that shift had not been directly observed.
In melanoma models, the newly reprogrammed macrophages stimulated the formation of new blood vessels inside tumors. That process, known as angiogenesis, is how tumors secure the oxygen and nutrients needed for rapid expansion. At the same time, the macrophages lost responsiveness to anti-cancer immune signals, effectively muting the immune response while simultaneously building the tumor’s infrastructure. The dual effect makes the subverted macrophages considerably more damaging than cells that simply fail to attack a tumor.
Alongside the behavioral changes, the reprogramming involves chromatin remodeling, meaning modifications to the packaging of DNA inside macrophage cells. Chromatin structure governs which genes are accessible for activation; its remodeling indicates that the tumor-driven changes are not surface-level responses but deep, epigenetic alterations that may persist as the macrophage continues functioning inside the tumor microenvironment. Whether those changes are reversible, and under what conditions, the study does not yet say.
“The better we understand these mechanisms, the better equipped we will be to develop treatments that block them and restore the immune system’s ability to fight cancer,” Dr. Cohen said. “This research points to a new and promising therapeutic target, one that focuses not only on the cancer cells themselves, but also on the processes that enable them to thrive.”
The team also analyzed data from patients with uveal melanoma, a cancer of the eye with a low survival rate when it spreads. In that dataset, patients whose tumors showed higher expression of the genetic signature the study identified in reprogrammed macrophages had significantly lower survival rates. The clinical correlation suggests the mechanism found in laboratory models is active in at least some human cancers, though the study does not specify sample sizes or whether the survival gap held across all stages of disease.
The macrophage-efferocytosis mechanism adds to a growing body of research showing that tumors manipulate the immune system from multiple directions. Last week, a study from McMaster University described a related pattern in glioblastoma, the most aggressive form of brain cancer, where a surface protein called GPNMB suppresses immune activity and protects tumors from destruction. CAR-T cell therapies are being developed to target that protein specifically. Whether comparable strategies could target the macrophage population identified in the Tel Aviv study is the question the research team is now positioned to explore.
Blocking efferocytosis entirely would not be a viable therapeutic approach. The process is essential for normal immune function and tissue maintenance throughout the body; inhibiting it would cause inflammation and widespread cellular accumulation. The research team’s focus is more specific: the genetic and epigenetic pathways activated inside macrophages after they consume dead cancer cells, rather than the cleanup process itself. That distinction matters for translation. A therapy that narrows its target to the reprogramming event, rather than the whole of macrophage efferocytosis, would have a substantially better safety profile than a broad inhibitor.
The Effero-seq technology may also have applications beyond this particular study. Tools that enable real-time observation of gene expression changes in immune cells after engulfment could be used to map analogous reprogramming events in other immune cell types or in other disease contexts. The study does not address that potential directly, but the development of such a tracking method is itself a contribution to the field, separate from the biological findings it produced in this study.
Researchers at Tel Aviv University and other institutions are now investigating the thymus and related immune organs as additional sites where cancer influences the body’s defenses. Earlier research from 2026 identified the thymus as a hidden driver of cancer outcomes through its role in shaping immune cell populations, a line of inquiry that overlaps with the macrophage reprogramming mechanism the new study describes, though the specific pathways differ.
What the Tel Aviv findings establish is that the tumor microenvironment exploits a process the immune system cannot avoid. Macrophages must clear dead cells. The tumor ensures that doing so costs them their independence.
