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Archive > Volume 24 Issue 6 > 2017,24(6):640-644. DOI:10.3872/j.issn.1007-385X.2017.06.011 Prev Next
Clinical Research
The patients with advanced esophageal cancer who carrying nonA5.1 type related MHC1 molecule A transmembrane region allele have high sensitivity to NK cell immunotherapy
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Abstract:
Objective:To investigate the effect of nonA5.1 type MHC class Ⅰrelated molecules A (MICA) transmembrane allele on the treatment efficacy of chemotherapy combined with NK cell immunotherapy in advanced esophageal cancer patients. Methods: One hundred and fiftytwo patients with advanced esophageal cancer (TNM ⅢⅣa) underwent systemic chemotherapy after palliative surgery between April, 2013 and October, 2015 were included in this study. According to whether the MICA transmembrane allele was A5.1, patients were divided into four groups to observe the clinical efficacy: A5.1 chemotherapy + NK cell therapy (A5.1+NK group); A5.1 chemotherapy alone (A5.1 group); nonA5.1 chemotherapy+NK cell therapy (non A5.1+NK group); nonA5.1 chemotherapy alone (non A5.1 group). Eukaryotic expression vector pTE1A5.1 carrying MICA allele A5.1 was constructed and used to transfect esophageal cancer TE1 cell line. Western blotting was used to detect the effect of pTE1A5.1 transfection on the expression of MICA protein in TE1 cells. The sensitivity change of TE1 cells to NK cells before and after the transfection was detected by LDH. ELISA was used to detect the soluble MICA in serum of esophageal cancer patients and the soluble MICA content in the supernatant of TE1 cells before and after transfection with pTE1A5.1. Results: After 3 years of followup, the medium overall survival (mOS) of A5.1+NK group, A5.1group, non A5.1+NK group and non A5.1 group were 15.0 months, 16.0 months, 22.4 months and 16.0 months, respectively. The mOS of non A5.1+NK group was significantly longer than that of other groups (P<0.05). There was no significant correlation between age, sex, ECOG score, genotype and prognosis by Cox multivariate regression analysis (P>0.05). The cross analysis of genotype and NK therapy showed that the mOS of non A5.1+NK group was significantly longer than that of the other three groups (P<0.05). The expression of MICA in TE1 cells was significantly increased after transfection with pTE1A5.1, and the soluble MICA secretion in culture supernatant was significantly increased (\[256.2±45.3\] vs \[45.3±11.5\] pg/ml, P<0.01). Compared with pretransfection, the killing rate of NK cells on TE1 cells overexpressing MICA was significantly decreased (\[29.5±7.2\]% vs \[42.5±7.1\]%, P<0.05).Conclusion: Compared with esophageal patients with MICAA5.1 allele, the efficacy of combined treatment of NK cell therapy and chemotherapy for patients with MICAnon A5.1 is better, which is closely related to low level of soluble MICA.
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Project Supported:
Project supported by the Young Backbone Talents Training of Health Systems of Fujian Province (No.2014ZQNJC7), and the Natural Science Foundation of Fujian Province (No.2015J01378，No.2015J01433
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