Supplementary Figure 10 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Distribution of LA and TLS across colorectal cancer sites.</p

Supplementary Figure 12 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Clustered heatmap of relative expression of proteins (GeoMX DSP) per ROI from CRCmetastatic tumor specimens (5 tumors/metastatic site).</p

Graphic Summary from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Graphic Summary</p

FIGURE 6 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Analysis of immune cells between paired primary and liver metastases. A, Representative images of the tumor core from two individual patient's paired primary colorectal cancer and metastatic liver tumors. B, Correlations of CD4 and CD8 T cells in the paired primary and liver metastases. R2 were calculated with the density of immune cells in different histologic regions.</p

Supplementary Figure 7 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Different antigen presentation potential CRC primary and metastatic tumors.</p

FIGURE 5 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Distribution of LA and TLS across colorectal cancer sites. A, Representative images of primary colorectal cancer tumor. Numbered insets show higher magnification. The second inset magnifies the same area seen in Fig. 1B. B, Representative images of primary and metastatic colorectal cancer tumors stained with mIF Panel 4. The boxes highlight the LA in the primary and metastatic tumors. C, Percentage of tumor specimens with intratumoral LA in primary and metastatic tumors. Statistical significance was determined by χ2 test. D, The number and percentage of area of LA in the metastatic tumor calculated in five individual compartments. E, Correlations of LA and various immune cells. PCC were calculated from the density LA and sporadic immune cells in different histologic regions from primary and metastatic colorectal cancer tumors from mIF Panel 4.</p

FIGURE 7 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Higher immune activity in lung metastasis, while more immune suppressive in the liver and peritoneal metastases. A, Representative image of ROI selection in GeoMx digital spatial profiling from a colorectal cancer lung metastasis. Cancer island and stroma within tumor core were identified by the expression of Pan-CK. Cell identity markers from metastatic colorectal cancer tumors (B) and markers highly expressing in the liver (C), lung (D), and peritoneal (E) metastases in GeoMx assay. Paired comparison of gene expression between each two organs in the different histologic regions shown in bottom row. F, GeoMx markers expressing in the LA. Statistical significance was determined by Wilcoxon signed-rank test for B–F.</p

Supplementary Figure 6 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Distribution of myeloid cells in the cancer island, stroma and necrosis tissue within tumor core and inner invasive region.</p

FIGURE 4 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Higher antigen presentation potential in lung metastases. A, Correlations of the immune cell density between histologic regions. PCC were calculated from the density of each immune cell type in different histologic regions. B, Representative images of primary and metastatic colorectal cancer tumors stained with mIF panel 4. The cancer cells, TCF1+ CD4 T cells, stem-like CD8 T cells and APCs were color coded and identified as Fig. 1C. The yellow dash lines indicate the boundaries between inner and outer invasive margin. C, Mean number of TCF1+ CD4 T cells and stem-like CD8 T cells around 10 µm radius of APCs and mean number of APCs around 10 µm radius of TCF1+ CD4 T cells and stem-like CD8 T cells. D, Paired comparison of cell density between each two organs in the different histologic regions. Statistical significance was determined by Wilcoxon signed-rank test. E, GSEA of liver and lung metastases samples from GES48468. Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to determine significantly modified pathways. Bars in red and blue represent, respectively, a positive and negative enrichment in the associated pathway. The x axis shows the normalized enrichment score (NES) of the analysis, and the y axis the enriched pathways. F, Heat map of top genes differentially expressed in GES48468 primary and metastatic colorectal cancer tumor samples from KEGG_ANITGENE_PROCESSING_AND_PRESENTATION pathway.</p

Supplementary Figure 11 from Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases

Analysis of immune cells between paired primary and liver metastases.</p