An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. (10.1038/s41586-023-06797-9 [doi])

These scientists wanted to understand how certain cells in our body can stop our immune system from fighting against cancer. They studied a type of cell called myeloid cells, which are known to suppress our body's ability to fight tumors. However, they didn't know exactly what causes these myeloid cells to become like this.

To find out, the scientists looked at both human and mouse lung cancer samples. They used a special technique called single-cell RNA sequencing to examine the genes in each individual cell. They discovered that a molecule called interleukin-4 (IL-4) is the main reason why myeloid cells become tumor-promoting and suppress our immune system.

To prove this, they used mice that had certain genes deleted. They found that when they removed the IL-4 receptor (a protein that IL-4 attaches to) from the early myeloid cells in the bone marrow, the tumors in the mice became smaller. But when they removed the IL-4 receptor from the mature myeloid cells, it didn't make any difference.

The scientists also wanted to see if they could use this information to help people with lung cancer. They started a clinical trial where they gave a drug called dupilumab, which blocks the IL-4 receptor, to patients with lung cancer who had already tried another treatment called PD-1/PD-L1 blockade. They found that when the patients took dupilumab along with the other treatment, some of them had a good response. Their tumors became smaller, and in one patient, the tumor disappeared completely.

This study is important because it shows that IL-4 is a key factor in making myeloid cells suppress our immune system in cancer. It also suggests that using a combination of drugs that block IL-4 and another treatment called immune checkpoint blockade could be a good way to fight cancer in humans. The scientists also realized that cancer affects our whole body, not just where the tumor is, so we need to come up with new ways to treat it.

LaMarche NM., Hegde S., Park MD., Maier BB., Troncoso L., Le Berichel J., Hamon P., Belabed M., Mattiuz R., Hennequin C., Chin T., Reid AM., Reyes-Torres I., Nemeth E., Zhang R., Olson OC., Doroshow DB., Rohs NC., Gomez JE., Veluswamy R., Hall N., Venturini N., Ginhoux F., Liu Z., Buckup M., Figueiredo I., Roudko V., Miyake K., Karasuyama H., Gonzalez-Kozlova E., Gnjatic S., Passegue E., Kim-Schulze S., Brown BD., Hirsch FR., Kim BS., Marron TU., Merad M. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature. 2024 Jan;625(7993):166-174. doi: 10.1038/s41586-023-06797-9. Epub 2023 Dec 6.