Small cell lung cancer (SCLC) is a particularly aggressive and fatal disease: fewer than 7 people out of 100 survive for five years.
One of the tricks SCLC uses to persist and evade treatment is to hide from the immune system. Now, an international team of researchers has found a way to remove this disguise and make SCLC more vulnerable.
Crucial to the new approach is a type of immune cell called a gamma delta T cell.
In a new study published in Cancer cellthe research team found that these immune cells could effectively kill SCLC cells in the laboratory – and their effectiveness was significantly improved when combined with two other existing drugs.
“These cells could provide an alternative route of immune attack on tumors, able to evade conventional cancer-fighting immune cells, opening up new possibilities for treating a cancer that has seen little progress in recent decades,” says molecular biologist Kate Sutherland, of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia.
Two previous significant clinical trials, IMpower133 and CASPIAN, put researchers on the trail of gamma delta T cells.
These trials tested approaches to immunotherapy for SCLC, and after analyzing the collected data, researchers found that patients with more evidence of gamma delta T cells responded better to treatments.
“It was striking that patients whose tumors contained more of these specialized immune cells often had better treatment outcomes,” says Sutherland.
“This is the strongest evidence to date that gamma delta T cells are present in small cell lung cancers and appear capable of fighting the disease.”
The team then carried out their own tests on the SCLC cells in the laboratory. While gamma delta T cells alone were reasonably effective cancer killers, the addition of the existing cancer drug tarlatamab captured many more cancer cells, bringing immune cells closer to their targets.
))>
Gamma delta T cells have also been shown to be better cancer fighters when combined with zoledronate, a drug already approved for the treatment of osteoporosis and cancer-related bone diseases.
Zoledronate increased the number of immune cells and helped them see through the “disguise” that SCLC usually relies on.
In some cases, it might eventually be possible to use a patient’s existing gamma delta T cells to grow more outside the body, then add them back to bolster the attacking forces against SCLC.
“For patients with lower gamma delta T cell levels, therapies such as zoledronate may offer a way to boost their anti-cancer immune cells and their responsiveness to treatments,” says WEHI’s Jin Ng.
“As there are already therapies that expand and reinfuse gamma delta T cells, our findings raise the exciting possibility of rapidly translating this discovery into new treatment strategies.”
There is much work to be done to develop therapies based on these findings, and the resulting treatments will not be effective in all cases of cancer. However, they could offer a powerful new anti-cancer drug option for many people with this stubborn type of cancer.
The study also suggests that the amount of gamma delta T cells already present in tumors, as well as the presence of a molecule called BTN2A1 – which acts as a sort of target marker for immune cells – could help predict how well a person responds to immunotherapy. The researchers want to explore this possibility.
Further research will require moving from laboratory testing to animal models, and eventually clinical trials on real cancer patients, which should tell us much more about the potential of gamma delta T cells as weapons against SCLC.
“For decades we have known that small cell lung cancer is exceptionally good at hiding from the immune system,” says Sutherland.
“We found an immune cell that appears to be able to see through this disguise.”
The research was published in Cancer cell.
This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. Although we are proud of our process, we are only human. If you spot an error, please let us know.
Gn Health
