Novel Therapeutic Approach Modifies Myeloid Cells to Stop Cancer Growth

Study suggests a new therapy could stop tumor growth by affecting myeloid cell behavior.

Researchers have developed a potential new therapeutic approach to stop tumor growth that works by affecting myeloid cell behavior in cancer, according to a new study published in Nature Communications.

Myeloid cells, a type of white blood cell, are typically recruited to either resolve infections and suppress tumor growth or promote tumor progression and wound healing. In cancer, tumors recruit harmful myeloid cells to help promote growth and suppress the activity of T cells. The study authors focused on a finding a potential treatment to disrupt this process.

For the study, the investigators examined integrin CD11b, a type of protein that helps myeloid cell migration and its ability to fight disease. According to the study, CD11b plays a critical role in regulating myeloid cells, but cancer tumors often inhibit them from promoting the development of disease-fighting T cells.

The researchers used a small molecule, leukadherin-1 (LA-1), to develop a therapy that can boost the function of CD11b to promote disease-fighting M1 type of myeloid cells. The M1 macrophage functions to suppress tumor growth, whereas the M2 macrophage help the cancer to grow and metastasize, the researchers noted.

By increasing CD11b activity, they aimed to create a microenvironment at the tumor site for T cells to enter and attack the cancer. For the study, 2 types of genetically altered mice were used to examine how modifying the CD11b activity affects myeloid cell behavior in cancer.

In mice that lacked CD11b, transplanted cancer tumors grew much larger than those in wild-type (normal) mice. In another experiment, the researchers used LA-1 to boost CD11b activity beyond its normal levels and discovered a signification reduction in tumor growth. The findings indicate that CD11b activity inhibits tumor growth, according to the authors.

To confirm that these results were directly due to LA-1, the researchers used a point mutation, which is a genetic mutation at a single residue in the CD11b protein sequence, according to the study.

“The boost in CD11b activity in the mouse with the point mutation mimics the one imparted on CD11b in normal mice with administration of LA-1,” study author Vineet Gupta, PhD, professor and vice chairperson for research and innovation in the Department of Internal Medicine at Rush Medical College, said in a press release about the findings.

According to the researchers, the study further showed that CD11b plays a critical role in regulating the polarization of myeloid cells into M1 or M2 macrophages. Without CD11b, the myeloid cells in tumors developed into the M2 sub-type.

Although the potential therapy shows promise, Dr Gupta concluded that that further research will be needed to eventually bring a treatment based on LA-1 to patients.

References

Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b activation drives anti-tumor innate immunity. Nature Communications. 2018. https://www.nature.com/articles/s41467-018-07387-4#Sec10.

Stopping Cancer from Recruiting Immune System Double Agents [news release]. Rush University Medical Center’s website. https://www.rush.edu/news/press-releases/stopping-cancer-recruiting-immune-system-double-agents. Accessed January 7, 2019.