Natural killer cells best for fighting lung cancer

By studying preclinical and patient samples of small cell lung cancer (SCLC), Australian researchers have revealed that natural killer (NK) immune cells — but not T cells — are essential for slowing the aggressive spread of lung cancer. Published in the Journal of Thoracic Oncology, the discovery offers hope for better treatments for people with SCLC.

SCLC is the most aggressive type of lung cancer, and is often detected after the disease has begun to spread, or metastasise. While people with SCLC will initially benefit from chemotherapy, these cancers rapidly develop resistance and the average patient survival is only a matter of months.

“New treatments are urgently needed for SCLC,” said Dr Sarah Best from the Walter and Eliza Hall Institute (WEHI). “There had been interest in harnessing the immune system to fight lung cancer — a line of treatment called immunotherapy. To date, T cell immunotherapies have been most investigated, but unfortunately these do not seem to help in SCLC.

“T cells are not the only cancer-fighting immune cell — NK cells can also attack tumour cells. Therefore, we decided to investigate which forms of immunotherapy might hold most promise for people with SCLC.”

Working with colleagues from WEHI and other Australian institutions, Dr Best started by looking at markers of anti-cancer immunity in patient SCLC samples. “We looked at tumours to understand which immune cells were present,” she explained.

“These analyses revealed that there is a wide variability between patients in the relative amounts of NK and T cells within tumours. The presence of these cells in tumours suggests there is an anti-cancer response underway.”

To understand whether NK or T cells could slow the spread of SCLC, the team looked at laboratory models of the disease that lacked either NK or T cells.

“We discovered that the loss of NK cells made SCLC tumours spread more, while the loss of T cells did not impact disease spread,” said WEHI researcher Jonas Hess. “This suggested that NK cells, but not T cells, are important for limiting metastasis of SCLC. Indeed, if we activated — or ‘supercharged’ — NK cells by adding the cytokine IL-15, they were even better at limiting SCLC spread.

“Activating T cells as well as NK cells further reduced SCLC spread, suggesting these two cell types can work together.”

WEHI researcher Dr Kate Sutherland said the study provides a clear rationale for pursuing NK cell-based immunotherapies as a potential treatment for SCLC. “To date, T cell-based immunotherapies have been advanced more for other cancers, but not for SCLC,” she said.

“Our study suggests that immunotherapies that harness NK cell’s tumour-fighting capabilities might be more effective for SCLC. We think NK cell-based immunotherapies could be an effective supplement to chemotherapy, slowing disease spread and extending the survival of SCLC patients.”

Some patients may benefit more from NK cell-based immunotherapies than others, Dr Sutherland added. “Bioinformatic analyses revealed a lot of variability in the amount of immune cells infiltrating patient SCLC tumours. We think this could mean that some SCLCs — those with more immune cell infiltration — could be particularly sensitive to NK cell-based immunotherapies.”

Image credit: ©stock.adobe.com/au/pabijan

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