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. 2015 Sep 15;5(10):3221-30.
eCollection 2015.

MHC I-related chain a expression in gastric carcinoma and the efficacy of immunotherapy with cytokine-induced killer cells

Yu Chen  1 , Jing Lin  2 , Zeng-Qing Guo  3 , Wan-Song Lin  4 , Zhi-Feng Zhou  4 , Chuang-Zhong Huang  4 , Qiang Chen  5 , Yun-Bin Ye  6
Affiliations

MHC I-related chain a expression in gastric carcinoma and the efficacy of immunotherapy with cytokine-induced killer cells

Yu Chen et al. Am J Cancer Res. .

Abstract

Cytokine-induced killer (CIK) cells have shown promising activity against gastric cancer in vitro and in vivo. Previous studies showed that cell signaling through MHC I-related Chain A (MICA)-Natural killer group 2, member D (NKG2D) results in CIK cell activation leading to cytolytic activities against tumor cells. In this study, we investigate the MICA status in patients with gastric carcinoma, and determine the potential relationship between MICA and clinical outcome of a CIK containing therapy. Two hundred and forty-three patients with gastric cancer who had received curative D2 gastrectomy were enrolled. The MICA expression of their tumors was determined by immunohistochemistry (IHC). Disease-free survival (DFS) and overall survival (OS) were evaluated. One hundred and forty-eight patients received adjuvant chemotherapy alone, and 95 patients received adjuvant chemotherapy combined with autologous CIK cell therapy. Patients who received adjuvant chemotherapy plus CIK had significantly longer DFS, 42.0 months vs. 32.0 months (P = 0.012), and OS, 45.0 months vs. 42.0 months (P = 0.039), by log-rank test. MICA high-expression, IHC scores of 5-7, was found in tumors from 89 of 243 patients (36.6%). The MICA expression was significantly correlated with the stage (P = 0.007) and there was a borderline association with histological grade (P = 0.054). In the adjuvant chemotherapy plus CIK group (n = 95), patients with high MICA expression had longer DFS, 46.0 months vs. 41.0 months (P = 0.027), and OS, 48.0 months vs. 42.0 months (P = 0.031). In the adjuvant chemotherapy alone group (n = 148), the median DFS and OS had no significant correlation with the MICA status. In a multivariate analysis stage, CIK therapy, and the interaction of MICA status and CIK therapy were independent prognostic factors for DFS and OS. Our study indicated that adjuvant chemotherapy plus CIK immunotherapy is a promising modality for treating gastric cancer patients after D2 gastrectomy. MICA status was associated with the outcome measures in CIK therapy, validation in prospective clinical trials is required to assess the value of this biomarker in the clinical decision-making process.

Keywords: Gastric cancer; MICA; NKG2D; adjuvant chemotherapy; cytokine-induced killer cells.

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Figures

Figure 1
Figure 1
MICA Staining by Immunohistochemistry in 243 patients with gastric cancer, showing the Scoring Patterns. A: a score of 0. B: a score of 3. C: a score of 7.
Figure 2
Figure 2
A: Kaplan-Meier estimates of Disease-Free-Survival (DFS) and Overall Survival (OS) in 243 patients. B: Kaplan-Meier estimates of DFS and OS for patients according to treatment group.
Figure 3
Figure 3
A: Kaplan-Meier estimates of DFS and OS for patients according to MICA status in 243 patients. B: DFS and OS for patients according to MICA status in patients received adjuvant chemotherapy plus CIK therapy group. C: DFS and OS for patients according to MICA status in patients received adjuvant chemotherapy alone group.
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