The following is a summary of “Multi-omic Characterization of Pancreatic Ductal Adenocarcinoma Relates CXCR4 mRNA Expression Levels to Potential Clinical Targets” published in the November 2022 issue of Clinical Cancer by Kocher et al.
The tumor microenvironment is thought to be significantly influenced by chemokines since they are crucial for immune cell trafficking. Poor differentiation, metastasis, and prognosis in pancreatic ductal adenocarcinoma are all linked to overexpression of CX-chemokine receptor 4 CX-chemokine receptor, and pancreatic ductal adenocarcinoma (PDAC). CXCR4 mRNA expression levels inside PDAC are characterized in detail in this work. CXCR4 mRNA expression in PDAC was studied for its potential molecular and immunologic significance using data from the Cancer Genome Atlas.
Validation and additional exploratory analyses were performed on a sizable (n=3,647) real-world dataset. Multiplex immunofluorescence (mIF) assays were conducted in-house, while single-cell RNA analysis were done on a publically available dataset, all with the goal of elaborating cellular localisation of CXCR4. Numerous immune-related genes, including immune checkpoint transcripts, were upregulated in conjunction with high CXCR4 mRNA expression (CXCR4 high), as was an increase in infiltration of regulatory T cells, CD8+T cells, and macrophages (e.g., TIGIT, CD274, PDCD1). Regardless of microsatellite instability status, mismatch repair status, or tumor mutational load, analysis of the validation cohort verified the CXCR4-dependent immunologic TME composition in PDAC.
CXCR4 was shown to be mostly expressed by macrophages and T-cell subsets, as determined by single-cell RNA analysis and mIF. An increased survival of CXCR4high PDAC provides more evidence for the clinical importance of our finding. A PDAC phenotype characterized by an abundance of T-cells and macrophages with highly expressed inhibitory immunological checkpoints is associated with high levels of intratumoral CXCR4 mRNA expression. Their results provide a possible basis for further study of CXCR4 as a prognostic biomarker in PDAC patients undergoing immune checkpoint suppression.