Renin-angiotensin inhibitors reprogram tumor immune microenvironment: A comprehensive view of the influences on anti-tumor immunity

// Dora L. Vallejo-Ardila 1 , Theodora Fifis 1 , Louise M. Burrell 2, 3 , Katrina Walsh 1 and Christopher Christophi 1 1 Department of Surgery, Austin Health, University of Melbourne, Melbourne,VIC 3084, Australia 2 Department of Medicine, Austin Health, University of Melbourne, Melbourne, VIC 3084, Australia 3 Department of Cardiology, Austin Health, University of Melbourne, Melbourne, VIC 3084, Australia Correspondence to: Dora L. Vallejo-Ardila, email: dvallejo@student.unimelb.edu.au Keywords: renin-angiotensin system; tumor microenvironment; anti-tumor immunity; kallikrein kinin system Received: June 26, 2018      Accepted: September 08, 2018      Published: October 26, 2018 ABSTRACT Renin-angiotensin system inhibitors (RASi) have shown potential anti-tumor effects that may have a significant impact in cancer therapy. The components of the renin-angiotensin system (RAS) including both, conventional and alternative axis, appear to have contradictory effects on tumor biology. The mechanisms by which RASi impair tumor growth extend beyond their function of modulating tumor vasculature. The major focus of this review is to analyze other mechanisms by which RASi reprogram the tumor immune microenvironment. These involve impairing hypoxia and acidosis within the tumor stroma, regulating inflammatory signaling pathways and oxidative stress, modulating the function of the non-cellular components and immune cells, and regulating the cross-talk between kalli krein kinin system and RAS.