NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?

Figure 1

New mechanism proposed for NK cell recruitment at melanoma tumor site. NK cells recognize melanoma cells through the interaction of NK activating receptors with their ligands (NKR-Ls) expressed on tumor cell (both depicted in dark blue). The resulting NK cell activation leads to the killing of melanoma cells (via perforin/granzyme B and induction of apoptosis) and to the active release of a chemotactic form of HMGB1 (green circles). Killed (apoptotic) cells passively release HMGB1 as oxidized molecule. However, this HMGB1 form has no chemotactic properties (purple circles). NK-derived reduced (i.e., all-thiol) HMGB1 can act as chemoattractant for activated NK cells through the engagement of RAGE (depicted in green), thus promoting their recruitment in the tumor microenvironment.