WEHI study reveals a new immune pathway for fighting small cell lung cancer

Researchers also showed existing drugs could be repurposed to boost the cancer-killing activity of these immune cells, opening new opportunities to strengthen current treatments and help more patients benefit from these therapies.

At a glance

Finding a way to boost treatment responses for lung cancer

Small cell lung cancer (SCLC) is one of the world's deadliest diseases, with a five-year survival rate of less than 7%.

Strikingly, patients whose tumors contained more of these specialized 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 tumors 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." Professor Kate Sutherland, senior author on the paper and WEHI laboratory headWe've found an immune cell that appears to be able to see through that disguise.

Using mini tumors to uncover a new lung cancer treatment strategy

To test whether gamma delta T cells could fight cancer, researchers created miniature tumors in the lab using samples generously donated by patients through the Victorian Cancer Biobank in collaboration with the Royal Melbourne Hospital. These "mini tumors" represent one of the most realistic laboratory models of SCLC developed to date.

When the team combined the mini tumors with gamma delta T cells taken from the patients' own blood, they found the immune cells were highly effective at recognizing and killing SCLC cells.

The researchers discovered they could amplify this immune response by using two existing drugs – tarlatamab (a cancer treatment approved for SCLC) and zoledronate (approved for osteoporosis and cancer-related bone disease).

The team found zoledronate increased the number of gamma delta T cells available and enhanced their ability to recognise SCLC tumors. Tarlatamab acted like a magnetic force that brought the immune cells into closer contact with the cancer.

Together, these drugs significantly enhanced the gamma delta T cells' ability to attack the cancer cells, suggesting a potential new way to strengthen anti-cancer immunity in SCLC.

Dr Jin Ng, first author on the paper, said the findings also raise the possibility of using existing gamma delta T cells for adoptive transfer therapies – where large numbers of these immune cells are grown outside the body and infused back into patients.

"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 personalized treatment approaches in small cell lung cancer and other solid cancers that are often missed by conventional immune cells."

Gathering clues from landmark immunotherapy clinical trials

Using advanced genomic and computational analyses led by WEHI's genomics and bioinformatics teams, researchers were able to link a strong gamma delta T cell signature to patients who experienced the greatest benefit from immunotherapy.

Source:

Walter and Eliza Hall Institute

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