CD11b is an integrin present on myeloid cells and normally helps myeloid cell migration and its ability to fight disease. In a new study, researchers found that CD11b promotes development of myeloid cells into one sub-type, the M1 macrophage, that functions appropriately to suppress tumor growth. However, the tumors often suppress CD11b activity that results in development of the myeloid cells into a different type of cell, the M2 macrophage. These cells actually ward off T cells, which are vital to fighting disease, and M2s also secrete growth factors and promote the development of new blood vessels that allow cancer to grow and metastasize.
The team explored how modifying the activity of CD11b affects myeloid cell behavior in the presence of cancer and whether that could be used as a novel strategy to treat cancers. Using a small molecule (leukadherin-1 [LA-1]) discovered in the laboratory of Vineet Gupta, Ph.D., Rush University Medical Center, the researchers developed a therapy that can boost the function of CD11b to promote the disease-fighting M1 type of myeloid cells, helping create a microenvironment at the tumor site where T cells can enter and attack the cancer.
The study used two types of genetically altered mice. One set of experiments was done with otherwise normal mice that lacked CD11b. Transplanted tumors grew much larger in those mice compared to the tumors in wild-type mice, suggesting that CD11b restrains tumor growth.
Further investigating the reason for this difference, the team found that CD11b plays a critical role in regulating the polarization of myeloid cells into M1 or M2 macrophages. In the absence of CD11b, most of the myeloids cells in tumors were the M2 sub-type, that help the tumor grow and spread.
Although LA-1 showed a great deal of promise, Gupta says it will be years before a treatment based on this molecule becomes available to patients.