Several studies demonstrate that these molecules are preferentially overexpressed on Treg in a range of human tumors.(71,72) In pre-clinical models, mAb targeting costimulatory receptors and engaging activating FcγR can deplete intratumoral Tregs and elicit anti-tumor CD8 T cell responses.(73) This TME effect clearly complicates the targeting of these molecules as should the mAb induce agonism of Tregs rather than depletion this could lead to their activation and expansion, thus restricting the anti-tumor response. This evidence concerns the gene FCGR2A and neoplasm.