Fig. 7: NK/ILC1-like cells expressing IL-35R are present in tumors and IL-35 is associated with poor prognosis in cancer. | Nature Communications

Fig. 7: NK/ILC1-like cells expressing IL-35R are present in tumors and IL-35 is associated with poor prognosis in cancer.

From: Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Fig. 7: NK/ILC1-like cells expressing IL-35R are present in tumors and IL-35 is associated with poor prognosis in cancer.The alternative text for this image may have been generated using AI.

a UMAP embedding of a pan-cancer single-cell RNA-seq atlas comprising 354,379 cells, encompassing both immune and non-immune populations following quality control, standard preprocessing, and upstream analysis. b Violin plots showing normalized expression levels of IL-35 subunit genes (EBI3 and IL12A) across selected immune cell populations. Expression values are plotted on a shared scale and populations are ranked in descending order based on their average expression level. c UMAP embedding of joint expression density for IL-35 cytokine genes, inferred using a Kernel Density Estimator (KDE) to capture co-expression of EBI3 and IL12A at the single-cell level. The joint density corresponds to the weighted average density of individual gene KDEs. d Violin plots displaying normalized expression levels of IL-35 receptor components (IL6ST, IL12RB2, and IL27RA) across selected immune cell populations. Expression values are plotted on a shared scale and populations are ranked by mean expression level. e UMAP embedding of joint expression density for IL-35 receptor combinations, inferred via Kernel Density Estimation (KDE) to assess co-expression of IL6ST with IL12RB2, IL6ST with IL27RA, and IL12RB2 with IL27RA. The joint density corresponds to the weighted average density of individual gene KDEs. f Violin plots showing enrichment scores of an ILC1-like transcriptional signature across immune cell populations of interest. Populations are ranked by module enrichment score. g Bubble map showing the correlation coefficient for EBI3 and IL12A in TCGA datasets: adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cervical carcinoma (CESC), cholangiosarcoma (CHOL), colorectal adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), kidney chromophobe carcinoma (KICH), kidney clear renal cell carcinoma (KIRC), kidney papillary cell carcinoma (KIRP), lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), mesothelioma (MESO), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), paraganglioma & pheochromocytoma (PCPG), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), sarcoma (SARC), skin cutaneous metastatic melanoma (SKCM), stomach adenocarcinoma (STAD), testicular germ cell cancer (TGCT), thyroid carcinoma (THCA), thymoma (THYM), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and uveal melanoma (UVM). Positive (green) and negative (red) correlation are highlighted, based on p-val<0.05. Dots size represents absR, Pearson correlation coefficient. h Patients from TCGA database were stratified as high or low for EBI3, IL12A, and IL12B based on the median and overall survival was analyzed in pan-cancer solid tumors data set. Kaplan-Meier survival curves for patients are represented and p-values were obtained with log-rank test. EBI3hi IL12Ahi IL12Blo were classified as IL-35+ and compared to other categories. i Patients from TCGA database (solid tumors only) were stratified as high or low for EBI3, IL12A, and IL12B based on the median and progression-free survival was analyzed in pan-cancer (solid tumors) data set. Kaplan-Meier survival curves for patients are represented and p-values were obtained with log-rank test. EBI3hi IL12Ahi IL12Blo were classified as IL-35+ group and compared to other categories.

Back to article page