CCR5 CCL5 gene expression in colorectal cancer comprehensive profiling and clinical value
Francesca Battaglin1, Yasmine Baca2, Joanne Xiu2, Anthony F. Shields3, Richard M. Goldberg4, Hiroyuki Arai1, JingyuanWang1, Priya Jayachandran1, Natsuko Kawanishi1, Annika Lenz1, Shivani Soni1, Andreas Seeber5,Jim Abraham2, Emil Lou6, Philip A. Philip3, Benjamin A. Weinberg7, Wu Zhang1, John L. Marshall7, W. Michael Korn2, Heinz-Josef Lenz1
Cytokine signaling plays a major role in modulating the tumor microenvironment (TME) promoting CRC progression.
The C-C motif chemokine ligand 5 (CCL5), one of the three ligands that bind to the C-C motif chemokine receptor 5 (CCR5), and the CCR5 receptor itself have been found to be over expressed in CRC, and elevated levels of CCL5 are linked to a poorer clinical outcome.
Signaling through CCR5 can enable tumor progression and metastasis through multiple mechanisms including cancer stem cell progression, increased angiogenesis, recruitment of immunosuppressive immune and stromal cells, and immunosuppressive polarization of macrophages within the TME.
We previously reported that genetic polymorphisms in CCL5 and CCR5 genes were significantly associated with treatment outcomes in patients with mCRC receiving anti-angiogenic and anti-EGFR treatment.
Here we aimed to characterize the molecular features associated with CCR5/CCL5 expression in CRC and whether CCR5/CCL5 levels could impact treatment outcome.