Reduce Secreted Gelsolin to Expose Cancer for Treatment

Researchers at Francis Crick Institute have identified a protein that helps tumors evade the immune system. And, in certain types of cancers, it is linked to a poorer chance of survival. The protein could become a target for future cancer treatments.

"The interaction between tumour cells, the surrounding environment and the immune system is a complex picture," says lead researcher Caetano Reis e Sousa in a press release issued by Francis Crick Institute. "And although immunotherapies have revolutionised the way certain cancers are treated, there's still a lot to understand about who is most likely to benefit."

"It's exciting to find a previously unknown mechanism for how our body recognises and tackles tumours. This opens new avenues for developing drugs that increase the number of patients with different types of cancer who might benefit from innovative immunotherapies."

A study is published in Cell. It reports that the researchers identified a protein called secreted gelsolin. It is present in blood plasma and is also secreted by cancer cells.

Dendritic cells hold debris from dead cancer cells on their surface to signal the presence of a tumor to nearby T-cells. But secreted gelsolin blocks a receptor inside dendritic cells, preventing them from alerting the killer T-cells of the immune system, which would kill the cancer cells if alerted. With no instruction passed to the T-cells, the tumors avoid their killer response.

"Dendritic cells play a vital role in the immune system and our body's response to cancer," explains researcher Evangelos Giampazolias. "Understanding this process in more detail will enable us to identify how cancers are able to hide and how we might remove their disguise."

The researchers analyzed clinical data and samples from patients with 10 different types of cancer. They found that individuals with liver, head, neck, and stomach cancers, who had lower levels of secreted gelsolin in their tumours, had higher chances of survival. They also found that blocking the action of secreted gelsolin in mice with cancer increased their response to treatments including checkpoint inhibitors, a major immunotherapy.

"While secreted gelsolin circulates in healthy blood plasma, some cancer cells secrete really high levels of it - so these tumours are launching an anti-immune defence which helps them avoid killer T-cells," explains researcher Oliver Schulz.

The researchers are persuaded that reducing levels of secreted gelsolin will allow dendritic cells to communicate their vital message that allows the immune system to fight cancer. So they plan to develop a potential therapy that targets the secreted gelsolin in cancer cells without affecting the activity of this protein in other parts of the body.

While curing cancer remains elusive, this research result shows that we are making slow but steady progress in uncovering the biology of cancer. And it encourages hope that effective general purpose cancer therapies will be eventually found.