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Review
. 2019 May;16(5):415-422.
doi: 10.1038/s41423-019-0224-2. Epub 2019 Mar 25.

Targeting natural killer cells in solid tumors

Guillaume Habif  1 , Adeline Crinier  2 , Pascale André  1 , Eric Vivier  1   2   3 , Emilie Narni-Mancinelli  4
Affiliations
Review

Targeting natural killer cells in solid tumors

Guillaume Habif et al. Cell Mol Immunol. 2019 May.

Abstract

Natural killer (NK) cells are innate lymphoid cells endowed with cytolytic activity and a capacity to secrete cytokines and chemokines. Several lines of evidence suggest that NK cells play an important role in anti-tumor immunity. Some therapies against hematological malignacies make use of the immune properties of NK cells, such as their ability to kill residual leukemic blasts efficiently after conditioning during haploidentical hematopoietic stem cell transplantation. However, knowledge on NK cell infiltration and the status of NK cell responsiveness in solid tumors is limited so far. The pro-angiogenic role of the recently described NK cell-like type 1 innate lymphoid cells (ILC1s) and their phenotypic resemblance to NK cells are confounding factors that add a level of complexity, at least in mice. Here, we review the current knowledge on the presence and function of NK cells in solid tumors as well as the immunotherapeutic approaches designed to harness NK cell functions in these conditions, including those that aim to reinforce conventional anti-tumor therapies to increase the chances of successful treatment.

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Conflict of interest statement

G.H., P.A. and E.V. are employees of Innate Pharma. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
NK infiltration in head and neck squamous cell cancer and lung small cell cancer samples Number of NKp46+ cells per mm2 measured by IHC in tumor samples and normal adjacent tissue (NAT) and percentage of tissue slice with NK cells are indicated (A and B, left panels). NK cells frequencies defined as CD45+, CD3−, CD56+, CD4− and/or CD14− among CD45+ leukocytes were measured in blood, NAT and tumor samples was by flow cytometry. The box and whiskers represent the maximum, 75 percentile, median, 25 percentile, and minimum. Each dot indicates a sample
Fig. 2
Fig. 2
Contour plots showing the positivity thresholds for indicated markers. NK cells were defined by flow cytometry as CD45+, CD3−, CD56+, CD4− and/or CD14− and represented by red contour plots. T cells defined as CD45+, CD3+, CD56− are represented in blue contour plots. Representative expression of several markers, on blood or tumor samples from head and neck squamous cell cancer and non-small cell lung cancer patients, exemplifying the staining and the positioning of the thresholds are shown
Fig. 3
Fig. 3
Expression profile of surface markers on NK cells from head and neck squamous cell cancer samples. NK cells were analyzed by flow cytometry and defined as CD45+, CD3−, CD56+, CD4− and/or CD14− in blood, normal adjacent tissue (NAT) and tumor samples. Frequencies of NK cells expressing indicated surface marker are shown. Box and whiskers represent maximum, 75 percentile, median, 25 percentile, and minimum. Each dot indicates a sample. For each marker the Wilcoxon test is used when matched data for the three kinds of samples were available, otherwise the Kruskal-Wallis test is used. Significant p-values below 0.05 are shown
Fig. 4
Fig. 4
Expression profile of surface markers in natural killer (NK) cells from lung small-cell cancer samples. NK cells were analyzed by flow cytometry and defined as CD45+, CD3−, CD56+, CD4− and/or CD14− in blood, normal adjacent tissue (NAT) and tumor samples. Frequencies of NK cells expressing the indicated surface markers are shown. Box and whiskers represent the maximum, 75 percentile, median, 25 percentile and minimum. Each dot indicates a sample. For each marker, the Wilcoxon test was used when matched data for the three types of samples were available; otherwise, the Kruskal–Wallis test was used. Significant p values below 0.05 are shown
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