Tumor MICA status predicts the efficacy of immunotherapy with cytokine-induced killer cells for patients with gastric cancer

• Published in: Immunologic research Vol. 64; no. 1; pp. 251 - 259
• Main Authors: Chen, Yu, Lin, Wan-song, Zhu, Wei-feng, Lin, Jing, Zhou, Zhi-feng, Huang, Chuan-zhong, Chen, Gang, Shi, Yi, Guo, Zeng-qing, Ye, Yun-bin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2016; Springer Nature B.V
• Subjects: Age Factors; Aged; Allergology; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Carcinoma - mortality; Carcinoma - pathology; Carcinoma - therapy; Chemotherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; Cytokine-Induced Killer Cells - immunology; Cytokine-Induced Killer Cells - transplantation; Female; Gastrectomy; Gastric cancer; Genes; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Humans; Immunology; Immunotherapy - methods; Internal Medicine; Male; Medicine/Public Health; Neoplasm Staging; Original Article; Prognosis; Proteins; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach Neoplasms - therapy; Studies; Survival Analysis; Treatment Outcome; Adjuvant chemotherapy; CIK; Gastric cancer; MICA
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-015-8743-0

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.