Journal: Cell Reports Medicine
Article Title: Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer
doi: 10.1016/j.xcrm.2025.102017
Figure Lengend Snippet: The spatial proximity of apCAFs and Tregs suggests potential communications between them (A) Representative multiplexed IF (mIF) pictures of pre, MPR, non-MPR lung tumors, showing the spatial distributions of APCs (CD74 + ) and Tregs (FOXP3 + ). Arrows indicate the interaction between Treg and apCAFs. For each group, at least 4 patients were included. Scale bar, 50 μm. (B) Representative mIF pictures showing the distributions of apCAFs (COL1A1 + CD74 + ) and Treg (FOXP3 + ). For each group, at least 4 patients were included. Arrows indicate the spatial distribution of Treg. Scale bar, 60 μm. (C) Scatterplot showing the relationships between the number of Tregs and apCAFs in (B), colored by groups. Only visions with comparable DAPI + cells were selected for calculation. Each dot represents a vision. For each group, at least 4 patients were included; for each patient, at least 3 visions with Tregs were selected randomly. The correlation coefficient is calculated by Pearson, and p value is determined by two-sided linear regression t test. (D) Violin plot showing the shortest distance of Treg to apCAFs/APC in (B). The shortest distance was determined by the distance between the apCAFs closest to a specific Treg. Only visions with comparable DAPI + cells were selected for calculation. Each dot represents a Treg cell. For each group, at least 4 patients were included; for each patient, at least 3 visions with Tregs were selected randomly; for each vision, every Treg was designated a shortest distance value. Significance was determined using unpaired Student’s t test. (E–G) (E) Boxplots showing the numbers of APCs within 25 μm radius centered around Tregs in (A). Only visions with comparable DAPI + cells were selected for calculation. (F) Boxplots showing the numbers of apCAFs within 25 μm radius centered around Treg in (B). Data are representative of three different experiments. (G) Boxplots showing the numbers of apCAFs/APCs within 25 μm radius centered around each Treg in (B). For (E)–(G), each dot represents a Treg cell. For each group, at least 4 patients were included; for each patient, at least 3 visions with Tregs were selected randomly; for each vision, at least one Treg was adopted to calculate the value. p value is calculated using unpaired Student’s t test. (H) UMAP plot of 9,363 CD4 + T cells colored by clusters in our NSCLC cohort. (I) UMAP plot of 13,893 CD4 + T cells colored by clusters in the GEO: GSE207422 cohort. (J) Heatmap showing the correlations between CD4 + T cells in our own CAF cohort and GEO: GSE207422 calculated by SingleR. (K) The proportions of CD4 + T cell clusters. Significance was determined using unpaired Student’s t test, and the absence of significance indicates no significant difference. ∗ p < 0.05, ∗∗ p < 0.01. (L) The proportions of IL-1R1_Treg in different efficacy groups from the GEO: GSE207422 cohort. p value is calculated by unpaired Student’s t test. (M) Network graphs representing the relative interaction strength between CAFs and CD4 + T cells (Treg and non-Treg). (N) Network graphs representing the interaction between CAFs (apCAFs and non-apCAFs) and CD4 + T cells. Edge strength represents the interaction strength calculated by CellChat. (O) Expression of FOXP3 and IL-1R1 in Treg and Tconv in GEO: GSE253540 datasets (left). Expression of FOXP3 and IL-1R1 in Treg, Tconv, and CD8 + T in PBMC of the healthy donors or NSCLC patients from GEO: GSE211044 datasets (middle, right). p value is calculated using unpaired Student’s t test. (P) Monocle trajectory inference for IL-1R1_Treg, LEF1_Treg, ANXA1_CD4, and CCR7_CD4, colored by cell states. Analysis was conducted on our own CAF scRNA-seq data. (Q) Proportion of cell state in each cluster.
Article Snippet: CD74 (D5N3I) XP® Rabbit mAb , CST , Cat# 77274; RRID: AB_2799893.
Techniques: Expressing
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