Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer.
Colorectal Cancer
MHC class I polypeptide-related sequence A
Natural killer cell
Regorafenib
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
20 Apr 2022
20 Apr 2022
Historique:
received:
25
12
2021
accepted:
04
04
2022
entrez:
21
4
2022
pubmed:
22
4
2022
medline:
23
4
2022
Statut:
epublish
Résumé
To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC. Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration-time curve of regorafenib, M2 and M5. Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045). MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment.
Sections du résumé
BACKGROUND
BACKGROUND
To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC.
METHODS
METHODS
Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration-time curve of regorafenib, M2 and M5.
RESULTS
RESULTS
Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045).
CONCLUSIONS
CONCLUSIONS
MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment.
Identifiants
pubmed: 35443621
doi: 10.1186/s12885-022-09512-5
pii: 10.1186/s12885-022-09512-5
pmc: PMC9019943
doi:
Substances chimiques
Biomarkers
0
Histocompatibility Antigens Class I
0
Phenylurea Compounds
0
Pyridines
0
regorafenib
24T2A1DOYB
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
428Informations de copyright
© 2022. The Author(s).
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