The Dual Role of Natural Killer Cells During Tumor Progression and Angiogenesis: Implications for Tumor Microenvironment-targeted Immunotherapies.

Immune cell polarization, as a consequence of their cellular plasticity has been described both for innate and
adaptive immunity. This cell polarization is finely tuned in cancers by several molecular mechanisms that
include cell-to-cell contact, interaction via soluble factors, and metabolic alterations/adaptations. The final
readout is the generation of immune cells with reduction of targeting/killing of tumor cells, tolerogenic/
immunosuppressive behavior, and acquisition of proangiogenic functions. Natural killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance. However, in solid malignancies, tumor-associated
NK cells (TANK cells, those in the peripheral blood) and tumor-infiltrating NK cells (TINK, those in tumor issues) show an altered phenotype and functions. Here, we discussed current state of the art on the dual role of
NK cells during tumor progression and angiogenesis, focusing on the tumor microenvironment-related factors
orchestrating NK cell polarization. Finally, we summarized current approaches used to manipulate/repolarize NK cells for immunotherapy approaches.