Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) say they have identified a previously overlooked type of immune cell that can recognise and kill small cell lung cancer (SCLC), one of the most aggressive forms of lung cancer.
The findings, published in Cancer Cell, link higher levels of gamma delta T cells in tumours with longer survival, suggesting these cells may play a role in shaping patient outcomes. SCLC has a five-year survival rate of less than 7%, and while immunotherapy has improved outcomes in some cancers, only a small subset of SCLC patients see long-term benefit.
WEHI said one reason SCLC has been difficult to treat is that tumours can be “invisible” to conventional immune cells targeted by existing immunotherapies. The institute’s study points to an alternative immune pathway that may be able to detect these cancers.
“For decades, we’ve known that small cell lung cancer is exceptionally good at hiding from the immune system,” said Professor Kate Sutherland, senior author on the paper and a WEHI laboratory head. “We’ve found an immune cell that appears to be able to see through that disguise.
“Strikingly, patients whose tumours contained more of these specialised immune cells often had better treatment outcomes.
“This is the strongest evidence yet that gamma delta T cells are present in small cell lung cancers and appear capable of fighting the disease.
“It suggests these cells may offer an alternative immune attack route for tumours that are able to evade conventional cancer-fighting immune cells, opening up new possibilities for treating a cancer that has seen few advances over the past decades.”
To test the cells’ activity, researchers created miniature tumours in the lab using samples donated by patients via the Victorian Cancer Biobank, in collaboration with the Royal Melbourne Hospital. When these models were combined with gamma delta T cells taken from the patients’ blood, WEHI said the immune cells were effective at recognising and killing SCLC cells.
The researchers also reported that two existing drugs could strengthen the immune response in the lab: tarlatamab, a cancer treatment approved for SCLC, and zoledronate, which is approved for osteoporosis and cancer-related bone disease. WEHI said zoledronate increased the number of gamma delta T cells and improved their ability to recognise tumours, while tarlatamab helped bring immune cells into closer contact with cancer cells.
Dr Jin Ng, first author on the paper, said the results also point to the possibility of using gamma delta T cells in adoptive transfer approaches, where immune cells are grown outside the body and infused back into patients.
“For patients with lower gamma delta T cell levels, therapies such as zoledronate may offer a way to boost their cancer-fighting immune cells and responsiveness to treatments,” Dr Ng said.
“As therapies that expand and reinfuse gamma delta T cells already exist, our findings raise the exciting possibility of rapidly translating this discovery into new treatment strategies.
“This could open an entirely new avenue for personalised treatment approaches in small cell lung cancer and other solid cancers that are often missed by conventional immune cells.”
WEHI said the team focused on gamma delta T cells after analysing data from the IMpower133 and CASPIAN clinical trials, which established immunotherapy as a standard treatment for SCLC. Using genomic and computational analyses, the researchers linked a strong gamma delta T cell signature to patients who experienced the greatest benefit from immunotherapy.
The institute said it is working with researchers at the Doherty Institute to translate the findings into a potential new class of immunotherapy drugs for SCLC.
The study, “γδ T cells modulate anti-tumor immunity in small cell lung cancer”, is published in Cancer Cell (DOI: 10.1016/j.ccell.2026.08.015).
