Researchers from Medical University of Vienna have identified a major mechanism that allows breast cancer tumours to escape the body’s immune system, opening the door for more effective immunotherapy treatments in the future.
The study, published in the journal Nature Communications, found that a biochemical process called sialylation plays a crucial role in suppressing immune activity inside breast tumours. The findings could help improve the response of breast cancer patients to immunotherapies such as checkpoint inhibitors, which currently show limited success in many cases.
According to the research team led by Stefan Mereiter and Josef Penninger, nearly two-thirds of breast tumours showed elevated levels of sialylation. This sugar-based modification on the surface of tumour cells reduces the ability of T-cells, the immune system’s cancer-fighting cells, to enter and attack the tumour.
The researchers analysed tissue samples from 136 breast cancer patients and observed that tumours with higher sialylation contained significantly fewer cytotoxic T-cells.
Further investigation revealed that sialylation increases the activity of G-CSF, an immunomodulatory growth factor produced by cancer cells. This process attracts immune-suppressive cells into the tumour environment, preventing effective immune responses and helping cancer cells remain hidden from the immune system.
Importantly, preclinical studies demonstrated that blocking sialylation pharmacologically restored immune activity within tumours. The inhibition allowed activated T-cells to spread throughout the tumour tissue while reducing the number of immunosuppressive neutrophil cells.
The researchers believe this approach could potentially overcome resistance to immunotherapy in breast cancer patients.
“Therapeutically blocking sialylation caused previously resistant tumour models to respond to immunotherapies,” the study authors noted, adding that targeted modulation of tumour sialylation may become a promising future strategy to enhance cancer immunotherapy effectiveness.
Breast cancer remains the most common cancer among women worldwide. While immunotherapies have transformed treatment outcomes in several cancers, their impact in breast cancer has been comparatively modest. The newly identified mechanism may therefore provide an important breakthrough for future treatment development.
The research team plans to continue exploring this therapeutic strategy through additional studies at the Department of Obstetrics and Gynaecology at Medical University of Vienna.
