Researchers may have opened a new treatment avenue for small cell lung cancer by identifying immune cells that recognize and kill the disease in laboratory models. The Cancer Cell study report from WEHI examined gamma delta T cells and a cancer that often escapes conventional immune detection.
Professor Kate Sutherland and Dr Jin Ng co-led the study. Patients whose tumors contained more gamma delta T cells often lived longer, an association that points to a possible immune response but does not show the cells caused longer survival.
Sutherland said the cancer had been known to hide from the immune system. “We’ve found an immune cell that appears to be able to see through that disguise,” she said.
Immune Cells Recognized Cancer in Laboratory Models
Small cell lung cancer, or SCLC, has a five-year survival rate of less than 7%, according to the study report. Immunotherapy has transformed outcomes for other cancers, but only a rare subset of people with SCLC experience long-term benefits. The researchers said one challenge is that SCLC can be difficult for conventional immune cells to detect.
The team analyzed data from the IMpower133 and CASPIAN clinical trials, which established immunotherapy as a standard treatment for SCLC. Genomic and computational analyses linked a strong gamma delta T cell signature to patients who experienced the greatest benefit from immunotherapy.
Researchers then created miniature tumors in the laboratory using patient samples donated through the Victorian Cancer Biobank, in collaboration with the Royal Melbourne Hospital. The source describes these mini tumors as among the most realistic laboratory models of SCLC developed to date. When the team combined them with gamma delta T cells taken from patients’ own blood, the cells recognized and killed SCLC cells in those experiments.
Existing Drugs Strengthened the Lab Response
The researchers tested tarlatamab and zoledronate in the laboratory models. Tarlatamab is an SCLC treatment, while zoledronate is approved for osteoporosis and cancer-related bone disease. The team reported that zoledronate increased the number of gamma delta T cells available and enhanced their ability to recognize SCLC tumors.
Tarlatamab brought the immune cells into closer contact with cancer cells, according to the study. Together, the drugs significantly enhanced the cells’ ability to attack cancer in the laboratory. These experiments do not establish that the combination is effective or safe for patients.
Dr Ng said the findings raise the possibility of adoptive transfer, in which large numbers of gamma delta T cells are grown outside the body and infused back into patients. He also said zoledronate may offer a way to boost cancer-fighting immune cells for patients with lower levels. These are proposed strategies, not treatments tested in patients by the mini-tumor experiments.
Clinical Translation Remains Ahead
The research team hopes to translate the findings into a new class of immunotherapy drugs for SCLC. That work is continuing with researchers at the Doherty Institute. The research received support from Cancer Council Victoria, the National Health and Medical Research Council (NHMRC), The CASS Foundation, and The International Association for the Study of Lung Cancer.
The study, “γδ T cells modulate anti-tumor immunity in small cell lung cancer,” was published in Cancer Cell (DOI:10.1016/j.ccell.2026.08.015).
