Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides. (https://www.nature.com/articles/s41586-023-06834-7)

These scientists did a study to understand how our immune system can fight against cancer. They found that there are special molecules in our body called peptides that can help our immune system recognize and attack cancer cells. These peptides are made by a special type of genetic material called circular RNA (circRNA). The scientists discovered that a specific circRNA called circFAM53B can make peptides that can help our immune system fight against breast cancer and melanoma.

To prove this, the scientists studied samples from people with breast cancer and melanoma. They used a special machine called mass spectrometry to find the peptides made by circFAM53B. They also looked at the genetic material in the cancer cells using a technique called ribosome sequencing. They found that the circFAM53B peptides were able to activate special immune cells called CD4+ and CD8+ T cells, which can help fight cancer.

The scientists also looked at patients with breast cancer and melanoma to see if the presence of circFAM53B and its peptides had any effect on their immune response and survival. They found that patients who had higher levels of circFAM53B and its peptides had more immune cells attacking the cancer cells and had better survival rates.

To understand how the circFAM53B peptides work, the scientists found that they can bind strongly to two important molecules in our body called HLA-I and HLA-II. These molecules help our immune system recognize and attack cancer cells. The scientists also tested their findings in mice with breast cancer and melanoma. They gave the mice vaccines made from circFAM53B or its peptides and found that the mice had more immune cells attacking the cancer cells, which helped control the tumors.

Overall, this study shows that circFAM53B, a special type of genetic material, can make peptides that activate our immune system to fight against breast cancer and melanoma. The scientists believe that using vaccines made from circFAM53B or its peptides could be a new way to treat cancer in the future.

Huang D., Zhu X., Ye S., Zhang J., Liao J., Zhang N., Zeng X., Wang J., Yang B., Zhang Y., Lao L., Chen J., Xin M., Nie Y., Saw PE., Su S., Song E. Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides. Nature. 2024 Jan;625(7995):593-602. doi: 10.1038/s41586-023-06834-7. Epub 2023 Dec 13.