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Review
. 2017 Mar 16:8:293.
doi: 10.3389/fimmu.2017.00293. eCollection 2017.

Role of Distinct Natural Killer Cell Subsets in Anticancer Response

Helena Stabile  1 , Cinzia Fionda  1 , Angela Gismondi  2 , Angela Santoni  3
Affiliations
Review

Role of Distinct Natural Killer Cell Subsets in Anticancer Response

Helena Stabile et al. Front Immunol. .

Abstract

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.

Keywords: hematological malignancies; natural killer cell subset; natural killer cells; solid tumors; tumor microenvironment.

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Figures

Figure 1
Figure 1
Shaping natural killer (NK) cell subsets in tumor microenvironment. The main cellular and soluble factors affecting NK cell subset distribution in tumor microenvironment are shown. Melanoma and AML are reported as examples of solid and hematological tumor, respectively. For melanoma, tumor and metastatic lymph node (M-LN) infiltrating NK cell subsets are represented. For AML, bone marrow and peripheral blood NK cell subpopulations are indicated.
See this image and copyright information in PMC

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