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| The pharmacogenomics journal. 2015 Mar 10. pii: tpj201514. doi: 10.1038/tpj.2015.14 |
| Variations in genes involved in immune response checkpoints and association with outcomes in patients with resected colorectal liver metastases. |
| Stremitzer S1, Sunakawa Y2, Zhang W3, Yang D4, Ning Y5, Stintzing S6, Sebio A7, Yamauchi S8, Matsusaka S9, El-Khoueiry R10, Stift J11, Wrba F12, Gruenberger T13, Lenz HJ14 |
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Abstract In patients with colorectal liver metastases (CLM), liver resection offers the possibility of cure and long-term survival. The liver is a highly immunogenic organ harboring ~80% of the body's tissue macrophages. Emerging data demonstrate a critical role of the immune response for cancer treatment. We investigated variations within genes involved in immune response checkpoints and their association with outcomes in patients with CLM who underwent neoadjuvant chemotherapy including bevacizumab and liver resection. Single-nucleotide polymorphisms (SNPs) in nine genes (CCL2, CCR2, LAG3, NT5E, PDCD1, CD274, IDO1, CTLA4 and CD24) were analyzed in genomic DNA from 149 patients with resected bevacizumab-pretreated CLM by direct Sanger DNA sequencing, and correlated with response, recurrence-free survival (RFS), overall survival (OS), probability of cure and recurrence patterns. IDO1 (indoleamine 2, 3-dioxygenase) rs3739319 G>A and CD24 rs8734 G>A showed a significant difference in 3-year OS rates. In addition, IDO1 rs3739319 G>A was significantly associated with extrahepatic recurrence. Recursive partitioning analyses revealed that IDO1 rs3739319 G>A was the dominant SNP predicting RFS and OS. Our data suggest that variants within genes involved in immune response checkpoints are associated with outcomes in patients with resected CLM and might lead to improved treatment strategies modulating anti-tumor immune response by targeting novel immune checkpoints.The Pharmacogenomics Journal advance online publication, 10 March 2015; doi:10.1038/tpj.2015.14. |
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Publikations ID: 25752522 Quelle: öffnen |
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