Cancer Resistance Through Cell Death Pathway

A new study has discovered an unanticipated route for cancer cells to evade the immune system, making treatments less effective. The study, published in Cancer Cell, describes how a type of cancer cell death might accelerate tumor growth by inhibiting the immune system’s ability to combat the malignancy.

Moffitt Cancer Center researchers studied a type of cell death known as necroptosis. Researchers discovered that cancer cells can emit interleukin-1α as they die, which was previously thought to aid the immune system in fighting cancer. This chemical contributes to an environment in the tumor that impairs the immune response, preventing T cells from fighting 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.”

Brian Ruffell, H. Lee Moffitt Cancer Center & Research Institute

The study discovered that cancerous cells secrete interleukin-1α in response to chemotherapy, which could explain why some therapies do not act as intended. Researchers found that inhibiting interleukin-1α improved the immune response and made cancer therapies more successful in animal models, including chemotherapy and immunotherapy.

“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.”

Lower levels of interleukin-1α have been associated to improved outcomes, particularly in chemotherapy patients. Interleukin-1α may serve as a predictor of cancer treatment efficacy for individual patients.

For more information: Hänggi, K., et al. (2024) Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity. Cancer Cell. doi.org/10.1016/j.ccell.2024.10.014.