Natural killer (NK) cells, the prototypic member of innate lymphoid cells, are important
effectors of anticancer immune response. These cells can survey and control tumor
initiation due to their capability to recognize and kill malignant cells and to regulate the
adaptive immune response via cytokines and chemokines release. However, several
studies have shown that tumor-infiltrating NK cells associated with advanced disease can
have profound functional defects and display protumor activity. This evidence indicates
that NK cell behavior undergoes crucial alterations during cancer progression. Moreover,
a further level of complexity is due to the extensive heterogeneity and plasticity of these
lymphocytes, implying that different NK cell subsets, endowed with specific phenotypic
and functional features, may be involved and play distinct roles in the tumor context.
Accordingly, many studies reported the enrichment of selective NK cell subsets within
tumor tissue, whereas the underlying mechanisms are not fully elucidated. A malignant
microenvironment can significantly impact NK cell activity, by recruiting specific subpopulations
and/or influencing their developmental programming or the acquisition of a
mature phenotype; in particular, neoplastic, stroma and immune cells, or tumor-derived
factors take part in these processes. In this review, we will summarize and discuss the
recently acquired knowledge on the possible contribution of distinct NK cell subsets in
the control and/or progression of solid and hematological malignancies. Moreover, we
will address emerging evidence regarding the role of different components of tumor
microenvironment on shaping NK cell response