Immune Microenvironment

Modulating the immune microenvironment

CSF1R-signaling pathway is responsible for the recruitment of the circulating monocytes to tumors, as well as their development into macrophage and further differentiation.1 Through a wide range of growth factors, cytokines and chemokines, the tumor microenvironment is thought to educate the tumor associated macrophages (TAMs) and determine their specific phenotype and hence functional role: tumorigenic or tumoristatic.1,2 In return, tumorigenic TAMs further support the tumor development using a variety of mechanisms including creating an immunosuppressive environment, production of mitogenic factors, as well as promoting angiogenesis, and degradation of the tumor extracellular matrix (thus aiding invasion and metastasis).3‑5 Inhibition of CSF1R signaling may be therefore of therapeutic relevance through modulation of the tumor microenvironment and enhancing of anti-tumor immune responses.6‑9 Subsequently, blocking the CSF1R signaling has been shown in preclinical studies to enhance sensitivity to immune response-stimulating agents, chemotherapy or radiation, potentially improving the effectiveness of related therapies.6‑10

  1. Noy R, et al. Immunity. 2014;41:49-61.
  2. Ostuni R, et al. Trends in Immuno. 2015;36:229-239.
  3. Lewis CE, et al. Cancer Res. 2006;66:605-612.
  4. Jinushi M, et al. Biochim et Biophys Acta. 2015;1855:123-130.
  5. Raggi C, et al. Oncogene. 2016;35:671-682.
  6. DeNardo DG, et al. Cancer Disc. 2011;1:54-67.
  7. Panni RZ, et al. Immunother. 2013;5:1075-1087.
  8. Ries CH, et al. Cancer Cell. 2014;25:846-859.
  9. Ruffell B, et al. Cancer Cell. 2014;26:623-637.
  10. Zhu Y, et al. Cancer Res. 2014;74:5057-5069.