Scientists at the University of Geneva have decoded the molecular mechanism by which solid tumors systematically reprogram the immune system's own frontline white blood cells — neutrophils — from cancer-killing defenders into cancer-promoting allies. The finding, published in Cancer Cell, explains a longstanding mystery in oncology: how tumors can grow aggressively even in patients with apparently strong immune systems, and why many immunotherapy treatments that look promising in early testing eventually fail.
Neutrophils are the most abundant white blood cells in human circulation and among the immune system's most aggressive early responders to infection and injury. Inside solid tumors, however, the research team found that a signaling molecule called TGF-beta, produced in abundance by cancer cells, systematically reprograms neutrophils into what the team calls a "pro-tumoral" state within days of their arrival in the tumor microenvironment.
From Defender to Enabler
Once reprogrammed, these tumor-associated neutrophils transform from cancer-killing cells into active tumor promoters. They release growth factors that stimulate the growth of new blood vessels feeding the tumor, suppress the cancer-killing activity of T cells, and secrete enzymes that help the tumor invade surrounding tissue and metastasize to other organs.
Crucially, the researchers found that blocking the TGF-beta signaling pathway with a small-molecule inhibitor in laboratory models reversed the neutrophil reprogramming. When this block was combined with a standard checkpoint inhibitor immunotherapy, tumor growth slowed dramatically more than with either treatment alone. Clinical trials testing the combination are expected to begin later in 2026, offering potential new hope for patients whose cancers have stopped responding to available immunotherapies.