NK cell activity is impaired in cancer patients, supporting the use of adoptive NK cell therapy, which is becoming a credible immunotherapy for hematological malignancies. This is even more so the case after the presentation of the first clinical study using anti-CD19 NK CAR cells, which showed a good clinical activity in the absence of toxicity. The possibility of targeting solid tumors is being studied by numerous laboratories, but the tumor microenvironment supports immune suppression. Unveiling the molecular and cellular mechanisms explaining this immunosuppression is a major goal.
For this special issue, we pointed to several specific subjects, such as the metabolic interactions of NK cells with tumor targets that would regulate their function or novel molecular strategies for generating off-the-shelf NK cell cancer immunotherapies. A total of 10 manuscripts have been accepted for publication, of which five are original research and five are reviews or minireviews. Regarding the original research articles, Alvarez et al. have described the indirect contribution of the PD-1/PD-L1 system to the regulation of NK cell exhaustion using an in vivo murine model. They showed that a PD-1 blockade increased CD8+ T cell activation rates, which competed for IL-2 and resources with NK cells, retarding their activation but also their subsequent exhaustion. Federici et al. developed an exhaustive work characterizing NK-cell derived extracellular vesicles (NKEVs), separating true exosomes from microvesicles..
