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.