How cancer cell death may harm the immune system and promote tumor growth

Researchers at Moffitt Cancer Center focused on a form of cell death called necroptosis. Previously thought to help the immune system fight cancer, researchers found that when cancer cells die in this way, they can release a molecule called interleukin-1α. This molecule helps create an environment in the tumor that weakens the immune response, preventing T cells from attacking the cancer.

"We thought necroptosis would help the immune system fight cancer, but instead, it seems to make things worse by helping tumors grow," said Brian Ruffell, Ph.D., associate member in the Immuno-Oncology Program at Moffitt and lead author of the study. "Our study shows that interleukin-1α is key to this process, and by blocking it, we might be able to help the immune system do its job."

The study also found that interleukin-1α is released by cancer cells responding to chemotherapy, which could explain why some treatments don't work as well as expected. But there's good news: By blocking interleukin-1α, researchers were able to improve the immune response and make cancer treatments like chemotherapy and immunotherapy more effective in animal models.

"By blocking the actions of interleukin-1α, we could make current cancer treatments more successful," said Ruffell. "Additionally, targeting interleukin-1α can reduce the toxicity associated with chemotherapy, meaning this approach could help patients respond to and better tolerate therapy."

Researchers also discovered that lower levels of interleukin-1α are linked to better outcomes, especially in patients treated with chemotherapy. This suggests that interleukin-1α could be used as a marker to predict how well cancer treatments might work for different patients.

This study was supported by the Swiss National Science Foundation Postdoctoral Fellowship (P2ZHP3_171892, P400PM_183881) National Institutes of Health (R01CA230610, P30-CA076292) and the Cancer Research Institute Lloyd J. Old STAR Award.