A team at Tel Aviv University has shown how tumors turn the body’s own cleanup crew into allies, redirecting immune cells whose day job is removing dead tissue into building new blood vessels and damping the anti-cancer defense. The study, published in Science Immunology in June 2026, introduces a method called Effero-seq that traces the switch in single macrophages, and it found that patients whose tumors carry the same molecular signature tend to survive less long. The work was led by Dr. Merav Cohen and doctoral students Roi Balaban and Ori Moskowitz at Tel Aviv University’s Gray Faculty of Medical and Health Sciences. Before Effero-seq, tools counted immune cells. The new method links each macrophage’s current molecular state to whether, and how recently, it has eaten a dead cell.
The Cleanup Crew in the Body’s Tissue
Macrophages are the immune cells whose day job is to swallow dead and dying cells. The act has a name: efferocytosis. It clears debris and quiets inflammation that would otherwise flare when cells die. Inside a tumor, the same routine plays out at a higher tempo, because cancer cells also die in large numbers as they grow.
Some prior work treated that tumor-internal cleanup as housekeeping, neutral or even helpful. The Tel Aviv University study argues the opposite, at least in the cancers the team examined. When macrophages engulf dead cancer cells, the meal doesn’t end with digestion, and the macrophage is reprogrammed in lasting ways that benefit the tumor.
How Effero-seq Traces the Switch
To see what changes inside a single macrophage after it eats a dead cell, the Cohen lab at Tel Aviv University built a tool called Effero-seq. The method pairs a pH-sensitive dye called pHrodo, which only fluoresces after a macrophage has acidified the lysosome that digests its cargo, with single-cell RNA sequencing that reads out which genes each cell is using. The first signal tells you the macrophage has been eating; the second tells you what the cell is becoming as a result. The two together let the team match each macrophage’s molecular state to whether and how recently it had performed efferocytosis, and to track that match over time rather than at a single snapshot. With that pairing in hand, the researchers could ask what a macrophage that just ate a dead cancer cell looks like, compared with a neighboring macrophage that had not. The full method is laid out in the Effero-seq paper in Science Immunology.
The team fed labeled dead cancer cells to macrophages and watched the response over time. They saw a specific set of genes gradually light up in proportion to how much cargo each cell had eaten, a pattern they named the effero-score. The same gene program appeared in macrophages sampled from mouse melanomas and, critically, in macrophages taken from human uveal melanoma tumors. The score is calculated cell by cell from the pHrodo signal, with brighter cells (more cargo eaten) showing higher effero-score values.
To produce that score, the Effero-seq pipeline runs through five steps in sequence. Each step depends on the previous one, from feeding the cells through sorting, sequencing, and scoring. The full method is detailed in the published paper.
- Macrophages are fed labeled dead cancer cells in culture or in a living tumor.
- The cells are stained with pHrodo, a dye that only fluoresces inside acidified lysosomes.
- Single macrophages are sorted by their pHrodo signal, a proxy for how recently they ate.
- Each sorted cell’s RNA is sequenced to read out its gene activity at that moment.
- Each cell is scored on the effero-score, the gene program tied to how much cargo it consumed.
Blood Vessels and a Quieter Immune Defense
When the team applied Effero-seq to a mouse melanoma model, two consequences stood out. Macrophages that had recently engulfed dead cancer cells clustered near existing blood vessels inside the tumor, in what the team calls spatial proximity to vascular niches. From that position, they began pumping out signals that promote the formation of new blood vessels. Each new vessel is a pipeline delivering oxygen and nutrients to a tumor that is otherwise running short of both. That lets the tumor grow faster than it otherwise would.
The second consequence was quieter and potentially more damaging. The reprogrammed macrophages showed altered chromatin accessibility, the physical packing of DNA that decides which genes a cell can turn on. That shift left them less responsive to interferon-gamma, the chemical signal the immune system uses to activate macrophages against tumors. In other words, the same cells that should have ramped up their attack on the tumor were being trained to stand down. The Tel Aviv University summary of the Effero-seq study notes that this altered state persists over time, suggesting the reprogramming is long-lasting rather than temporary.
Why Patients With Higher Scores Fare Worse
The team extended the work beyond mouse models by analyzing tumors from patients with uveal melanoma, a form of eye cancer. They asked whether human tumors show the same molecular pattern the effero-score captures, and whether that pattern tracks with how patients fare. The answer to both questions was yes, with patients whose tumors carried a higher expression of the effero-score tending to survive less long.
That correlation does not, on its own, prove that the effero-score is driving the worse outcomes. Tumors are messy environments and many signals vary together, so the finding is a hypothesis to test, not a verdict. What it does establish is that the same molecular program the team identified in mice is also present in real patients. It is also prognostically meaningful in the cohort the team analyzed.
For now, the clinical signal rests on a single study in a single cancer type, uveal melanoma, and the team has not yet published survival numbers in a larger or independent cohort. What the paper does show is that the effero-score behaves in patient tumors the way it behaves in mice. The human data came from analyzing tumors that had already been collected and characterized, not from a new prospective trial. The paper does not establish that the effero-score is driving the worse outcomes, only that it tracks with them.
- Cancer type: uveal melanoma, a form of eye cancer
- Cohort signal: higher effero-score expression tracks with shorter survival
- Status: single study, awaiting replication in independent cohorts
A New Kind of Target for Cancer Therapy
The immediate payoff of the work is a new way to ask questions about tumor immunology. Existing methods can count macrophages, or profile their gene activity in bulk, but Effero-seq couples that profile to a specific recent action: eating a dead cell. That linkage matters because it gives researchers a handle on which macrophages in a tumor have been reprogrammed and which have not, which is the kind of distinction a treatment would need to make.
The longer-term question is whether blocking efferocytosis in tumors, or reversing its effects on macrophages, can slow cancer growth. Dr. Cohen frames the work as a starting point for that effort, not a finished therapy. Her team’s emphasis is on macrophages and on the efferocytosis process as targets, in addition to the cancer cells themselves. In a published statement, she pointed to a new therapeutic target focused on the processes that enable tumors to thrive. The study itself stops short of testing any treatment.
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. 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.
Dr. Cohen, the senior author of the study, made the point in published remarks. The mouse model and patient cohort together establish what the effero-score looks like in tumors where it matters. The next step, as the team describes it, is preclinical work that tests whether blocking efferocytosis slows tumor growth and reshapes the immune landscape. None of the work in the paper has moved to clinical trials yet.
Clinical translation remains a hypothesis. Whether such treatments can be developed, and whether they will work in patients, are open questions the study itself does not answer. Until those tests run, the survival finding in this paper’s patient cohort is the only direct human evidence that the macrophage reprogramming has clinical consequences.
It is also the finding that most needs to be replicated in independent cohorts before the field treats it as a clinical signal. For now, the Cohen team’s contribution is the effero-score itself, and the Effero-seq method that measures it.
Frequently Asked Questions
What is efferocytosis?
Efferocytosis is the process by which macrophages and other phagocytes swallow and digest dead or dying cells. It is a normal housekeeping task that keeps tissue healthy and prevents the inflammation that would otherwise flare up when cells die. The Tel Aviv University study focuses on what happens to macrophages that perform efferocytosis inside a tumor. The team found that the process does not end with the meal; it reprograms the cell.
What is Effero-seq?
Effero-seq is a method developed by the Cohen lab at Tel Aviv University that links a single macrophage’s recent efferocytic activity to its current gene activity. It pairs a pH-sensitive dye called pHrodo with single-cell RNA sequencing, letting researchers identify macrophages that have just eaten a dead cell and read out what those cells are doing at the molecular level.
Could this lead to new cancer treatments?
Dr. Cohen, the senior author, describes the work as pointing to a new therapeutic target, but the research is preclinical. The team’s next steps involve testing whether blocking efferocytosis can slow tumor growth in mice. The paper itself does not describe clinical trials in humans. Whether any will follow depends on results from those next-stage studies.
Is the finding only about melanoma?
The Cohen team’s Effero-seq findings have so far been tested in a mouse melanoma model and in tumors from patients with uveal melanoma, a form of eye cancer. The paper does not address whether the same reprogramming signature holds in other cancer types. That question would require separate studies in other tumor types, which the team has not yet reported.
What is the effero-score?
The effero-score is the gene program the Cohen team defined to capture how a macrophage’s molecular state changes with efferocytosis. It is the set of genes that turn on in proportion to how much dead-cell cargo a macrophage has consumed, and the team found the same program in macrophages from human uveal melanoma tumors whose patients had shorter survival.
How does the effero-score relate to patient survival?
In the Cohen team’s patient cohort, higher expression of the effero-score in tumor macrophages was correlated with shorter survival. The finding has not yet been replicated in independent cohorts. Until that replication happens, the correlation should be read as a hypothesis, not a clinical rule. The Cohen team’s contribution is the effero-score itself and the Effero-seq method that measures it.
Why does this finding matter?
The finding matters because it ties a routine immune process to two specific tumor-fueling outcomes: new blood vessel growth and a dampened anti-cancer immune response. It also provides a measurable gene program, the effero-score, that correlates with patient survival in uveal melanoma. It points to a new set of treatment targets, including the efferocytosis process itself and the chromatin changes downstream of it.
