New Insights into Treating Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a notably aggressive form of cancer, with fewer than 7% of patients surviving five years after diagnosis. One of the clever tactics SCLC employs is its ability to mask itself from the immune system, allowing it to thrive and resist treatment. Fortunately, a group of international researchers has discovered a method to strip away that disguise, potentially making SCLC more susceptible to therapies.

The key player in this new strategy is a type of immune cell known as gamma delta T cells. In a recent study published in Cancer Cell, the research team revealed that these immune cells can effectively target and eliminate SCLC cells in laboratory settings. Their findings indicated that the cells’ cancer-fighting power increased significantly when combined with two already available drugs.

“These cells could provide an alternative way to attack tumors that successfully evade typical cancer-fighting immune cells, which opens up fresh avenues for treating a cancer that, frankly, hasn’t seen much progress in recent years,” states Kate Sutherland, a molecular biologist at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia.

Two major clinical trials, IMpower133 and CASPIAN, initially led researchers to investigate gamma delta T cells. These trials focused on immunotherapy methods for SCLC, and after analyzing the data, it became apparent that patients displaying more gamma delta T cells tended to have better responses to treatments.

“Interestingly, we found that patients with higher levels of these specialized immune cells often experienced more favorable treatment outcomes,” Sutherland adds. “This provides strong evidence that gamma delta T cells are present in small cell lung cancers and seem capable of combating the disease.”

The team conducted their own experiments using SCLC cells in a lab environment. While gamma delta T cells showed promise as standalone cancer killers, incorporating the existing drug tarlatamab allowed for the capture of more cancer cells, facilitating a greater interaction with the immune cells.

Moreover, gamma delta T cells proved to be more efficient when combined with zoledronate, a medication already approved for conditions like osteoporosis and cancer-related bone issues. Zoledronate not only increased the number of immune cells but also helped them see through the disguise that SCLC typically relies on.

Eventually, there may be a possibility of utilizing a patient’s own gamma delta T cells to cultivate more of them outside the body and then reintroduce them to enhance the attack against SCLC. “For patients with lower levels of gamma delta T cells, therapies like zoledronate could provide a pathway to amplify their immune cell responses and effectiveness with treatments,” remarks Jin Ng from WEHI.

“Given that there are existing therapies to expand and reinfuse gamma delta T cells, our findings present an exciting possibility of quickly turning this discovery into new treatment strategies.” While significant progress remains to be made in developing therapies based on these insights, it’s clear that these approaches might provide a powerful new option for individuals facing this challenging type of cancer.

Additionally, the study suggests that the quantity of gamma delta T cells within tumors, along with the presence of a molecule called BTN2A1—which acts as a target for immune cells—could potentially help predict how well patients respond to immunotherapy. The researchers are keen to further explore this angle.

Taking the research further will necessitate moving from laboratory settings to animal studies, and ultimately to clinical trials involving actual cancer patients, which will better illuminate the potential of gamma delta T cells as a treatment weapon against SCLC.

“For a long time, we’ve recognized that small cell lung cancer has a remarkable ability to camouflage itself from the immune system,” Sutherland notes. “Now, we’ve identified an immune cell that seems capable of looking past that disguise.”

The research findings were published in Cancer Cell.