CXCR2 and CXCR4 cytokine receptors are known to be expressed by immune inhibitory cells such as neutrophils, myeloid derived suppressor cells (MDSCs), and Tregs. Cytokine signalling from the pancreatic cancer microenvironment attracts these cells which then prevent CD8+ and CD4+ T cells from engaging with the tumour. It has been found that targeting the CXCR2 and CXCR4 signalling axis in mouse models of pancreatic cancer can make checkpoint inhibitor therapy effective which, unfortunately, normally does not reduce pancreatic tumour volume due to the inhibitory microenvironment [1,2].
The following CXCR4 and CXCR2 clinical trials may be of relevance to pancreatic cancer:
- Steele, Colin W., Saadia A. Karim, Joshua D.G. Leach, Peter Bailey, Rosanna Upstill-Goddard, Loveena Rishi, Mona Foth, et al. ‘CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma’. Cancer Cell, June 2016. doi:10.1016/j.ccell.2016.04.014.
- Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, Teichmann SA, Janowitz T, Jodrell DI, Tuveson DA, Fearon DT. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20212-7. doi: 10.1073/pnas.1320318110. PubMed PMID: 24277834.