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

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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.

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Acknowledgments

We thank everyone at our institution who helped with this study. The project was supported by the Foundation of the Natural Science Foundation of Fujian Province (Grant No. 2015J01435), the Medical Innovation Foundation of Fujian Province (Grant No. 2015-CX-9), and the National Clinical Key Specialty Construction Program.

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Authors and Affiliations

  1. Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Teaching Hospital, No 420, Fuma Road, Fuzhou, 350014, Fujian Province, People’s Republic of China

    Yu Chen, Jing Lin & Zeng-qing Guo

  2. Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Teaching Hospital, No 420, Fuma Road, Fuzhou, 350014, Fujian Province, People’s Republic of China

    Wan-song Lin, Zhi-feng Zhou, Chuan-zhong Huang & Yun-bin Ye

  3. Department of Pathology, Fujian Provincial Cancer Hospital, Fujian Medical University Teaching Hospital, Fuzhou, Fujian Province, People’s Republic of China

    Wei-feng Zhu, Gang Chen & Yi Shi

  4. Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, People’s Republic of China

    Yu Chen, Wan-song Lin, Zhi-feng Zhou, Chuan-zhong Huang, Gang Chen, Yi Shi, Zeng-qing Guo & Yun-bin Ye

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  1. Yu Chen
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Correspondence to Zeng-qing Guo or Yun-bin Ye.

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Chen, Y., Lin, Ws., Zhu, Wf. et al. Tumor MICA status predicts the efficacy of immunotherapy with cytokine-induced killer cells for patients with gastric cancer. Immunol Res 64, 251–259 (2016). https://doi.org/10.1007/s12026-015-8743-0

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