Whole blood interferon‐γ levels predict the therapeutic effects of adoptive T‐cell therapy in patients with advanced pancreatic cancer

  • Takeshi Ishikawa
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Satoshi Kokura
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Naoyuki Sakamoto
    Iseikai Hyakumanben Clinic Kyoto Japan
  • Tetsuya Okayama
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Masahiro Endo
    Iseikai Hyakumanben Clinic Kyoto Japan
  • Reiko Tsuchiya
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Manabu Okajima
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Tatsuzo Matsuyama
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Satoko Adachi
    Department of Cancer ImmunoCell Regulation Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Kazuhiro Kamada
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Kazuhiro Katada
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Kazuhiko Uchiyama
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Osamu Handa
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Tomohisa Takagi
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Nobuaki Yagi
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Takashi Ando
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Kazuko Uno
    Louis Pasteur Center for Medical Research Kyoto Japan
  • Yuji Naito
    Department of Molecular Gastroenterology and Hepatology Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan
  • Toshikazu Yoshikawa
    Department of Cancer ImmunoCell Regulation Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto Japan

書誌事項

公開日
2013-03-29
資源種別
journal article
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/ijc.28117
公開者
Wiley

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説明

<jats:p>A core challenge in administering immune‐based treatments for cancer is the establishment of easily accessible immunological assays that can predict patients' clinical responses to immunotherapy. In this study, our aim was to predict the therapeutic effects of adoptive T‐cell therapy in patients with advanced pancreatic cancer. To do this, we evaluated whole blood cytokine levels and peripheral regulatory T cells (Tregs) in 46 patients with unresectable or recurrent pancreatic cancer who received adoptive T‐cell therapy at 2‐week intervals. To test immune function, venous blood was obtained from patients before the start of therapy and 2 weeks after the 4th treatment. Whole blood interferon (IFN)‐α levels (after stimulation with the Sendai virus) were evaluated, as well as the levels of 9 cytokines stimulated with phytohemagglutinin [interleukin (IL)−2, IL‐4, IL‐5, IL‐10, IL‐12(p70), IL‐13, tumor necrosis factor‐α, IFN‐γ, and granulocyte‐monocyte colony‐stimulating factor]. Peripheral Tregs were analyzed by flow cytometry. Using the obtained data, we then observed the relationship between these immunological parameters and clinical outcome of patients. We found that the whole blood production of IFN‐γ, IL‐2, IL‐4, IL‐5 and IL‐13 significantly increased after adoptive T‐cell therapy, whereas the number of peripheral Tregs did not change. Multivariate Cox proportional hazards analyses indicated that the number of peripheral Tregs before receiving adoptive T‐cell therapy and the change in IFN‐γ levels after adoptive T‐cell therapy were independent variables predicting overall survival. The findings of this study indicate that the assay of whole blood IFN‐γ production offers promise for evaluating the clinical response of patients to cancer immunotherapy.</jats:p>

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