Australian researchers discovered a type of immune cells that can kill small cell lung cancer (SCLC). When combined with existing drugs like zoledronate and tarlatamab, these immune cells significantly improved treatment outcomes, offering a new therapeutic strategy for patients who don’t respond to conventional immunotherapy.
- Gamma delta T cells can penetrate the immune evasion mechanisms of small cell lung cancer and attack tumor cells directly.
- Patients with higher levels of gamma delta T cells showed better responses to immunotherapy in clinical trials Impower133 and CASPIAN.
- This discovery opens possibilities for adoptive transfer therapies and personalized treatment approaches for patients with low gamma delta T cell levels.
Researchers in Australia have uncovered a previously overlooked immune cell that can detect and kill small cell lung cancer (SCLC) — the deadliest form of the disease globally. Their paper, “γδ T Cells Modulate Anti-Tumor Immunity in Small Cell Lung Cancer,” was published in Cancer Cell.
The study, which was conducted at the Walter and Eliza Hall Institute of Medical Research (WEHI), explored why only a small number of SCLC patients respond to immunotherapy and how to increase responsiveness.
“For decades, we’ve known that small cell lung cancer is exceptionally good at hiding from the immune system. We’ve found an immune cell that appears to be able to see through that disguise,” said senior author and WEHI laboratory head Kate Sutherland in a WEHI news release. “Strikingly, patients whose tumors contained more of these specialized immune cells often had better treatment outcomes.”
Researchers developed lab-grown miniature tumors using patient samples donated from the Victorian Cancer BioBank, in collaboration with the Royal Melbourne Hospital. The team said the tumors were the most true-to-life laboratory models of SCLC to date.
Next, the researchers put the immune cell type — gamma delta T cells — to the test. They combined the cells, which were taken from patient blood samples, with the mini tumors and observed the cells identify and attack SCLC cells.
They also found two existing drugs that could boost the immune response: tarlatamab (an approved treatment for SCLC) and zoledronate (an approved treatment for osteoporosis and bone-related cancer). Zoledronate improved the gamma delta T cells’ ability to recognize the cancerous tumors, while Tarlatamab demonstrated a magnetic effect, moving the gamma delta T cells closer to the cancerous cells.
Together, the drugs significantly enhanced the likelihood of the gamma delta T cells at ridding SCLC, researchers said. The entire discovery, they noted, opens the door to a new therapeutic strategy for patients who have SCLC.
“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.” Sutherland said. “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 few decades.”
The study’s findings also suggest the prospect of adoptive transfer therapies, said first author Jin Ng, MD. This is a process where gamma delta T cells could be grown in the lab and infused back into SCLC 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,” he said. “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.”
Prior to the study, the research team analyzed data from two clinical trials that led to establishing immunotherapy as a standard treatment for SCLC: Impower133 and CASPIAN. Investigators from WEHI’s genomics and bioinformatics team used advance genomic and computational analysis, which identified a strong correlation between patients with positive responses to immunotherapy and patients with high levels of gamma delta T cells.
Sutherland and Ng said they hope the study informs the development of a new class of immunotherapy drugs for SCLC that can be put into clinical application.
