Pancreatic tumours are typically non-immunogenic and those containing so called M2, CD68, CD163 or CD204 positive tumour associated macrophages (TAMs) have a poor prognosis . M1 TAMs are considered to function immunologically against the tumour whereas M2 actively suppress the immune system in the tumour environment. There is a continuous spectrum of macrophage phenotypes between the polar opposites of M1 and M2. Promoting an M1 macrophage phenotype would be highly desirable in pancreatic cancer.
Two secreted cytokines play a role in maintaining the balance: GM-CSF can drive macrophage polarisation to M1 whereas CSF-1 can drive M2 polarisation. Antibodies targeting the macrophage receptor for CSF-1 (CSF-1R) can block the M2 phenotype and tip the balance towards M1 (figure 1) . Several companies including Bristol-Myers Squibb, Roche, and Lilly have anti-CSF-1R antibodies in phase I clinical trial for solid tumours including pancreatic.
|Figure 1: In the balance. Credit: synx508. No changes were made. Creative Commons Attribution-NonCommercial 2.0 Generic (CC BY-NC 2.0).|
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