Tilting the balance towards tumour associated macrophage (TAM) M1 with anti-CSF-1R

Version française

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 [1]. 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) [2]. Several companies including Bristol-Myers Squibb, Roche, and Lilly have anti-CSF-1R antibodies in phase I clinical trial for solid tumours including pancreatic.

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Figure 1: In the balance. Credit: synx508. No changes were made. Creative Commons Attribution-NonCommercial 2.0 Generic (CC BY-NC 2.0).

Refs

  1. Kurahara, Hiroshi, Hiroyuki Shinchi, Yuko Mataki, Kousei Maemura, Hidetoshi Noma, Fumitake Kubo, Masahiko Sakoda, Shinichi Ueno, Shoji Natsugoe, and Sonshin Takao. ‘Significance of M2-Polarized Tumor-Associated Macrophage in Pancreatic Cancer’. The Journal of Surgical Research 167, no. 2 (15 May 2011): e211–19. doi:10.1016/j.jss.2009.05.026.
  2. Ries, Carola H., Michael A. Cannarile, Sabine Hoves, Jörg Benz, Katharina Wartha, Valeria Runza, Flora Rey-Giraud, et al. ‘Targeting Tumor-Associated Macrophages with Anti-CSF-1R Antibody Reveals a Strategy for Cancer Therapy’. Cancer Cell 25, no. 6 (June 2014): 846–59. doi:10.1016/j.ccr.2014.05.016.
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