Fig. 1: An active IDO/TDO-Kyn-AHR pathway associates with immune suppressive features in human cancers. | Nature Communications

Fig. 1: An active IDO/TDO-Kyn-AHR pathway associates with immune suppressive features in human cancers.

From: Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine

Fig. 1

a Top: heat-map representing the gene-expression analysis of Kyn-degrading enzymes (KMO, KYNY, HAAO) and KD-Score (grayscale) in responsive (complete response/CR or partial response/PR) highlighted in black (n = 8), or non responsive (stable disease/SD or progressive disease/PD) highlighted in gray (n = 31), melanoma patients after PD-1 blockade. Bottom: bar graph with quantification of KD-Score. b ELISA quantification of L-Kynurenine in blood serum of melanoma patients (left) categorized as IDOhigh or IDOlow (n = 4 IDOhigh and n = 4 IDOlow) based on intracellular IDO staining by FACS of melanoma cell suspensions (right) (n = 8 IDOhigh and n = 10 IDOlow). c mRNA of immunoregulatory markers by qRT-PCR analysis in IDOhigh and IDOlow melanoma cell suspensions. d mRNA of AHR-target genes CYP1A1 and CYP1B1 by qRT-PCR analysis in IDOhigh and IDOlow melanoma cell suspensions after treatment with selective AHR inhibitor KYN-101 for 24 h (n = 6 IDOhigh and n = 6–7 IDOlow). e Distribution of log-transformed expression levels of AHR-related genes (TDO2, AHR, and CYP1B1) across six immune subtypes of cancer (C1: wound-healing, C2: IFN-γ dominant, C3: inflammatory, C4: lymphocyte-depleted, C5: immunologically quiet, C6: TGF-β dominant). Data plotted as box and whiskers with the median and limits within the 10–90% percentile. f Correlation analysis between Treg marker (FOXP3), myeloid-cell marker (MRC1/CD206), inhibitory checkpoint (PDCD1/PD-1), and AHR-related genes IDO1, TDO2, and CYP1B1 in TCGA RNAseq data of skin melanoma (SKCM), squamous lung (LUSC) and pancreatic adenocarcinoma (PDAC) analyzed by Spearman rank correlation. Data shown are represented as mean values ± SEM with two-tailed unpaired Student’s t test in (ad), one-way ANOVA test with Tukey correction in (a) and Kruskal–Wallis with Dunn correction in (e). P value: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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