Abstract
Tumor immune microenvironment plays a crucial role in tumor progression. We performed immune profiling to compare immune-related gene expression between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast using nCounter PanCancer immune Profiling Panel and found that CXCL10 was the most significant gene that had the highest difference in expression between them. Effect of CXCL10 on breast cancer cell proliferation and invasion was examined in vitro, and expression of CXCL10 and its relationship with immune cell infiltration was assessed in breast cancer samples. CXCL10 induced cell proliferation, migration and epithelial-mesenchymal transition in MCF-7 and MDA-MB-231 breast cancer cell lines. We confirmed that CXCL10 mRNA expression was significantly higher in invasive carcinoma than in DCIS, especially in hormone receptor (HR)-negative tumors using a validation set. CXCL10 mRNA expression showed a positive correlation with tumor infiltrating lymphocyte (TIL) density in both DCIS and invasive carcinoma; CXCL10-positive tumors generally showed higher infiltration of CD8+ and FOXP3+TILs as well as PD-L1+ immune cells compared to CXCL10-negative tumors, albeit with different patterns according to HR status. In conclusion, our study showed that CXCL10 promotes tumor cell proliferation, invasion, and immune cell infiltration, implying its contribution in the progression of DCIS to invasive carcinoma of the breast.
Highlights
Tumor immune microenvironment plays a crucial role in tumor progression
We evaluated the immune microenvironment of ductal carcinoma in situ (DCIS) in comparison with invasive breast cancer focusing on tumor infiltrating lymphocyte (TIL) subsets and PD-L1+ immune cells[7]
Immune Profiling Panels including 770 immune-related genes, the difference in immune-related gene expression was evaluated in DCIS and invasive carcinoma using the first set of samples including 16 cases of DCIS and 32 cases of invasive carcinoma
Summary
Tumor immune microenvironment plays a crucial role in tumor progression. We performed immune profiling to compare immune-related gene expression between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast using nCounter PanCancer immune Profiling Panel and found that CXCL10 was the most significant gene that had the highest difference in expression between them. Our study showed that CXCL10 promotes tumor cell proliferation, invasion, and immune cell infiltration, implying its contribution in the progression of DCIS to invasive carcinoma of the breast. Chemokines are small proteins, usually between 8 and 10 kDa, that provide leukocytes with directional cues for development, homeostasis, and inflammation through interaction with a subset of seven-transmembrane G protein-coupled receptors (GPCRs)[4] Their role as a pro-inflammatory mediator that attracts leukocytes at the site of inflammation is well known, and chemokines have been considered a potential target for inflammatory diseases and autoimmune d iseases[5,6]. We evaluated the immune microenvironment of ductal carcinoma in situ (DCIS) in comparison with invasive breast cancer focusing on tumor infiltrating lymphocyte (TIL) subsets and PD-L1+ immune cells[7]. We examined the association of CXCL10 expression with TIL density and immune cell subset infiltration in DCIS and invasive carcinoma of the breast. Gene (mRNA) CXCL10 LAG3 IL32 CXCL9 PDCD1LG2 CD96 SH2D1A CD5 TAP1 HLA-DRA CCL5 STAT1 PLAU HLA-DPA1 C1S CXCR4 BIRC5 CK1 VCAM1 CXCL2
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