Abstract
In this study, we determine the relationship between the expression of major histocompatibility complex class I chain-related gene A (MICA) in gastric cancer tumors after D2 gastrectomy and the clinical outcome of a CIK-containing adjuvant therapy. Ninety-five consecutive patients with gastric cancer after D2 gastrectomy who received adjuvant chemotherapy combined with CIK cell therapy were enrolled. The MICA expression of their tumors was determined by immunohistochemistry (IHC). High expression of MICA protein was documented by IHC in 38 of 95 tumor samples (40.0 %). The MICA status was significantly associated with the age and stage, p = 0.008 and 0.023, respectively. Analysis of NKG2D on in vitro expanded CIK cells showed that the percentages of NKG2D+ in CD3+/CD56+, CD3−/CD56+, and CD3+/CD8+ cells populations were 97.2 ± 1.4, 97.9 ± 1.8, and 95.6 ± 2.1 %, respectively. For patient with high MICA-expressing tumors, the median DFS and OS were longer than for the patients with tumors with low expression of MICA; 46.0 versus 41.0 months (p = 0.027), and 48.0 versus 42.0 months (p = 0.031), respectively. In a multivariate analysis, stage and MICA expression were independent prognostic factors for DFS and OS. Our findings show that adjuvant chemotherapy plus CIK therapy treatment is a promising modality for treating gastric cancer patients after D2 gastrectomy. Especially, those who have tumors with high expression of MICA were more likely to benefit from such a treatment strategy. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.
Highlights
Accumulating evidence has demonstrated that cytokineinduced killer (CIK) cell immunotherapy may improve outcomes when used as an adjuvant to current standard treatment
Previous studies showed that cell signaling through MHC I-related Chain A (MICA)-Natural killer group 2, member D (NKG2D) results in CIK cells activation leading to cytolytic activities against tumor cells
From January 2009 to March 2012, ninety-five consecutive patients with gastric cancer after D2 gastrectomy who received adjuvant chemotherapy combined with CIK cell therapy were enrolled (Table 1)
Summary
Accumulating evidence has demonstrated that cytokineinduced killer (CIK) cell immunotherapy may improve outcomes when used as an adjuvant to current standard treatment. Previous studies showed that cell signaling through MHC I-related Chain A (MICA)-Natural killer group 2, member D (NKG2D) results in CIK cells activation leading to cytolytic activities against tumor cells. We determine the relationship between the expression of MICA in gastric cancer tumors after D2 gastrectomy and the clinical outcome of a CIK containing adjuvant therapy
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