Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne have identified a rare type of immune cell that can recognize and kill small cell lung cancer (SCLC), the most aggressive form of the disease. The study, published in Cancer Cell, points to gamma delta T cells as a potential foundation for a new class of immunotherapy.
The team built miniature tumors in the lab using samples from the Victorian Cancer Biobank and the Royal Melbourne Hospital, then exposed them to gamma delta T cells drawn from the same patients' blood. The immune cells proved highly effective at detecting and destroying the cancer cells. Separately, the researchers mined data from two major immunotherapy trials, IMpower133 and CASPIAN, and found that patients whose tumors carried a stronger gamma delta T cell signature tended to survive longer after treatment.
Evading detection
Small cell lung cancer accounts for roughly one in seven lung cancer diagnoses and is notoriously hard to treat because tumor cells frequently shut down the MHC-I molecules that conventional T cells rely on to spot a threat. Gamma delta T cells work differently, detecting signs of cellular stress rather than MHC-I, which may let them flag tumors that have otherwise gone invisible to the immune system.
Senior author Kate Sutherland said the cells offer a way around that evasion.
"We've found an immune cell that appears to be able to see through that disguise."
Kate Sutherland, Walter and Eliza Hall Institute
The researchers also tested whether existing drugs could enhance the effect. Zoledronate, a drug normally used for bone conditions, increased the number of gamma delta T cells and sharpened their ability to recognize tumors, while tarlatamab, an approved lung cancer immunotherapy, helped draw the immune cells into closer contact with cancer cells. First author Jin Ng said the drug combination points toward a near-term treatment strategy.
"Therapies such as zoledronate may offer a way to boost their cancer-fighting immune cells."
Jin Ng, Walter and Eliza Hall Institute
Still preclinical
The findings are preclinical: the tumor-killing results come from lab-grown tissue and biobank samples, not from treating patients, and the survival link drawn from the IMpower133 and CASPIAN datasets is an association rather than proof that gamma delta T cells caused the better outcomes. The WEHI team says it now hopes to move the work toward adoptive cell therapy, in which a patient's own gamma delta T cells would be grown outside the body and infused back in, but no clinical trial of the approach has yet begun.
