Fig. 1
From: NK cells and solid tumors: therapeutic potential and persisting obstacles
Environmental obstacles against optimal NK cell activity in solid tumors. For optimal anticancer effects, adoptively transferred natural killer (NK) cells must (1) access and abundantly infiltrate the tumor microenvironment, (2) persist and proliferate therein in the context of preserved NK cell-activating receptor expression and limited NK cell-inhibiting receptor expression, and (3) ultimately mediate potent secretory and cytotoxic functions. Moreover, malignant cells must retain expression of NK cell-activating ligands and sensitivity to the cytotoxic activity of NK cells. Defects in NK cell trafficking as well as environmental parameters including (but not limited to) hypoxia, reactive oxygen species (ROS), prostaglandin E2 (PGE2) secretion and extracellular adenosine abundance interfere with one or several of these sine qua non, ultimately limiting (and hence representing valid targets to improve) the therapeutic effects of adoptively transferred NK cells against solid tumors. CCL5, C-C motif chemokine ligand 5; CXCL, C-X-C motif chemokine ligand; CX3CL1, C-X3-C motif chemokine ligand 1; DC, dendritic cell; MDSC, myeloid-derived suppressor cell; TAM, tumor-associated macrophage; TEFF, effector T; TREG, regulatory T