Based on previous reports that mild hypoxia, e.g. induced by blockade of vascular endothelial growth factor A, augments the activation and effector phenotype and functions of CD8 + T cells by initiating the HIF1α program [36, 42, 43], and on our own new finding that a hypoxia-mimetic agent significantly enhances the cytolytic capacity of gene-engineered CAR T cells, we have reason to hypothesize that procoagulatory effects of even small amounts of tTF-NGR in tumor vessels may create mild hypoxic conditions for superior CAR T cell activity within the TME. This evidence concerns the gene CD8A and neoplasm.