Fig. 5: The CXCL12/CXCR4 signaling pathway impairs autophagy and functionality in NK cells.
From: C/EBPβ-dependent autophagy inhibition hinders NK cell function in cancer
A Volcano plot showing the fold change expression of autophagy genes between tumor-conditioned and control NK cells (n = 2 biological replicates, NK cells from different mice). B–D Flow cytometry analysis of CXCR4+ cells in tumor-conditioned vs control NK cells (B, n = 7 biological replicates, independently collected batches of tumor-conditioned medium), Ptenpc+/+ vs Ptenpc−/− prostate-infiltrating NK cells (C, n = 6 Ptenpc+/+ mice and n = 5 Ptenpc−/− mice) and tumor vs non-tumor infiltrating NK cells (D, n = 5 samples/group). E UMAP representation of the 24 major cell types identified within CD45+ and CD45− infiltrating cells in Ptenpc−/− tumor tissues (n = 2 Ptenpc+/+ mice and n = 2 Ptenpc−/− mice). F CellPhoneDB intercellular communication analysis between NK cells and all the other cell clusters identified by scRNA-seq (n = 2 Ptenpc+/+ mice and n = 2 Ptenpc−/− mice). G Graph showing the autophagic flux on murine NK cells in tumor-conditioned NK cells, with or without Plerixafor (n = 5 biological replicates, independently collected batches of tumor-conditioned medium). H Cytotoxicity of tumor-conditioned NK cells, with or without Plerixafor, against YAC-1 target cells (n = 4 biological replicates, independently collected batches of tumor-conditioned medium). I Graph showing the autophagic flux on murine NK cells, in presence or absence of CXCL12 (n = 4 biological replciates, NK cells from different mice). J Cytotoxicity of control or CXCL12-treated NK cells against YAC-1 target cells (n = 5 biological replicates, NK cells from different mice). K Graph showing the autophagic flux on non-targeting (NT) and CXCR4 KO NK-92 cells, upon tumor-conditioned medium exposure (n = 5 biological replicates, independently collected batches of tumor-conditioned medium). L Cytotoxicity of NT and CXCR4 KO NK-92 cells, exposed to tumor-conditioned medium, against PC3 target cells (n = 12, biological replicates, data pooled from two independent experiments). M, N Tumor growth curves (M) and tumor volume at the end of the experiment (N) referred to mice treated as described in 4 G (n = 7 control, n = 7 NT NK-92 cells, n = 7 CXCR4 KO NK-92 cells). O Graph showing the absolute number of tumor-infiltrating NK-92 cells. n = 7 control, n = 7 NT NK-92 cells, n = 7 CXCR4 KO NK-92 cells. P, Q Flow cytometry analysis of effector functions in tumor-infiltrating (P) and circulating (Q) NK-92 cells. n = 7 control, n = 7 NT NK-92 cells, n = 7 CXCR4 KO NK-92 cells. Data in (A) are presented as volcano plot; two-tailed unpaired t test. Data in (B), (C), (G–L), and (O–Q) are presented as Min to Max box-and-whisker plot, the box extends from the 25th to 75th percentiles and the whiskers reach the sample maximum and minimum values, the median is indicated at center line and the mean value is indicated as “+”; two-tailed unpaired t test. Data in (D) are presented as as before-after plot; two-tailed paired t test. Symbols in (M) represent mean and error bars indicate SEM; one-way ANOVA test, comparing area under the curve (AUC). Data in (F) are presented as balloon plot; enriched ligand–receptor interactions were calculated based on permutation test. Data in (N) are presented as Min to Max box-and-whisker plot, the box extends from the 25th to 75th percentiles and the whiskers reach the sample maximum and minimum values, the median is indicated at center line and the mean value is indicated as “+”; one-way ANOVA test with Holm-Šídák’s multiple-comparisons test.
