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. 2024 Jan 24;15:683. doi: 10.1038/s41467-024-44789-z

Fig. 5. NK cells in human CRC show loss of effector functions.

Fig. 5

Evidence for dysfunctional NK cells within human CRC was sought through bioinformatics analysis of publicly available data sets alongside flowcytometric analysis of primary human CRC samples. A UMAP of 3521 NK cells from scRNA-seq of 62 human CRC samples, from GSE178341. B Expression of selected marker genes for clusters shown in ‘A’. C Expression of ITGAM and ITGA1 in NK1 subsets. D Granzyme and perforin gene expression in NK1 subsets, in tumor (T) versus normal adjacent (N) tissue. E Gene set enrichment for KEGG Natural killer cell-mediated cytotoxicity between NK1 clusters. F Gaussian kernel density embedding of cells in CRC tumors by tumor staging, and (G) lymph node (LN) metastases. H Representation flow plots depicting the frequency of CD49a+ and CD11b+ NK cells across PBMC, unaffected colon tissue and CRC primary tumor for the same donor. I Bar plot showing the frequency of CD11b+ CD49a-, CD11b- CD49a- and CD11b- CD49a+ NK cells across compartments. J Ratio of CD11b+ CD49a- to CD11b- CD49a+ NK cells across tissue compartments. K Representative histograms showing expression of selected markers on tumor infiltrating NK cell subsets. L Bar plots depicting geoMFI values for specific markers in tumor infiltrating NK cells. Statistical significance was determined by: (E) two-sided Wilcoxon rank-sum test, data are shown as box (median; box, 25th percentile and 75th percentile; whiskers, 1.5*inter-quartile range) and violin plots, (I) two-way ANOVA with Tukey’s multiple comparison test, and (J, L) Friedman test with Dunn’s multiple comparisons test. Data are presented showing all individual data points as well as the mean value +/- SD. H–L describe data from 10 patients with colorectal cancer, where n = 10 and ‘n’ defines an individual patient.