Interactions with between immune cells and tumor cells have become a large focus in cancer research. A central question in this field revolves around how monocytes and macrophages differentiate into either an M1 subtype, which supresses cancer progression, or an M2 subtype, which enhances it.
Very little is known about the immune microenvironment in pituitary tumors, but a recent study from the laboratory of UCSF neurosurgeon Manish Aghi, MD, PhD, has shown that more aggressive non-functioning pituitary adenomas (NFPAs) release more of the protein MCP-1, which in turn recruits more M2 macrophages and leads to a more invasive phenotype. NFPAs with low levels of MCP-1 expression, but elevated levels of GM-CSF protein, had more macrophages that differentiated into the M1 subtype.
Interestingly, MCP-1 expression began to taper off as more M2 macrophages were recruited to the tumor site, suggesting a possible negative feedback loop that eventually restricts uncontrolled tumor growth. M2-induced NFPA proliferation was found to be mediated by EZH2 and S100A9, and the study’s authors propose that these may be valid therapeutic targets for NFPAs that cannot be completely resected.
This is the first study to report an association between tumor-associated macrophage subtype and NFPA behavior. While NFPAs are typically slow-growing and benign, some forms can be more aggressive, causing vision loss, hypopituitarism, and severe headaches.
Authors: Additional authors of this paper were Garima Yagnik, PhD, Martin Rutowski, MD, and Sumedh Shah, PhD.