Variations in genes involved in immune response checkpoints and association with outcomes in patients with resected colorectal liver metastases.
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.
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Surgery, Medical University Vienna, Vienna, Austria.
S
S
Stremitzer
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Y
Y
Sunakawa
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
W
W
Zhang
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
D
D
Yang
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Y
Y
Ning
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
S
S
Stintzing
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
A
A
Sebio
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
S
S
Yamauchi
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
S
S
Matsusaka
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
R
R
El-Khoueiry
Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria.
J
J
Stift
Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria.
F
F
Wrba
Department of Surgery I, Rudolfstiftung Hospital, Vienna, Austria.
T
T
Gruenberger
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
H-J
HJ
Lenz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
D000068258:Bevacizumab