Figure 2 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages

Spatial heterogeneity of the immune microenvironment correlates with patient prognosis in human colorectal cancer. A, Representative images of defined seven cell types (CD8⁺PD-1⁺TIM-3⁺, CD8⁺PD-1⁺TIM-3⁻, CD8⁺PD-1⁻TIM-3⁻, CD8⁻PD-1⁺TIM-3⁺, CD8⁺PD-1⁻TIM-3⁺, CD8⁻PD-1⁺TIM-3⁻, and CD8⁻PD-1⁻TIM-3⁺). B, Combination of the distance map and cell subtype map showed spatial infiltration patterns. Criteria of spatial division of the tumor: i.t. (within 10 μm to the tumor cell), proximal (10–30 μm to the tumor cell), and distal (more than 30 μm to the tumor cell). C, Representative image of microenvironment regions and different infiltration patterns of three-marker–defined CD8⁺ T cells. D, Hierarchical clustering of all quantified immune cells and their spatial phenotypes. Heatmap represents z-score–normalized data; red color represents expression above the mean, blue color represents expression below the mean, and white color represents the mean. E, Representative image and spatial state of three subtypes: cluster 1, high-infiltrated; cluster 2, medium-infiltrated; and cluster 3, low-infiltrated, characterized by infiltration of CTLs; blue color represents cells at a distance of 0 μm from the tumor cells, and yellow color represents cells at a distance of 30 μm from the tumor cells. F, K–M curve (log-rank test) survival plots depict the OS in the unsupervised clusters. DAPI,x; mid, medium.