Adoptive cellular therapy enhances the helper T cell response and reduces the number of regulatory T cells

Ishikawa,Takeshi; Kokura,Satoshi; Sakamoto,Naoyuki; Matsumoto,Tsuguhiro; Funaki,Jun; Adachi,Satoko; Okayama,Tetsuya; Uchiyama,Kazuhiko; Handa,Osamu; Takagi,Tomohisa; Yagi,Nobuaki; Ando,Takashi; Uno,Kazuko; Naito,Yuji; Yoshikawa,Toshikazu

doi:10.3892/etm.2011.271

Adoptive cellular therapy enhances the helper T cell response and reduces the number of regulatory T cells

Authors:
- Takeshi Ishikawa
- Satoshi Kokura
- Naoyuki Sakamoto
- Tsuguhiro Matsumoto
- Jun Funaki
- Satoko Adachi
- Tetsuya Okayama
- Kazuhiko Uchiyama
- Osamu Handa
- Tomohisa Takagi
- Nobuaki Yagi
- Takashi Ando
- Kazuko Uno
- Yuji Naito
- Toshikazu Yoshikawa
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Affiliations: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 603-8151, Japan, Iseikai Hyakumanben Clinic, Kyoto, Japan, Louis Pasteur Center for Medical Research, Kyoto, Japan
Published online on: May 12, 2011 https://doi.org/10.3892/etm.2011.271
Pages: 737-743

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Abstract

It remains to be clarified whether adoptive cellular therapy (ACT) in patients with advanced cancer, in whom strong immunosuppression and immune-escape mechanisms are established, has the potential to alter cytokine secretion from blood cells and affect the number of regulatory T cells (Tregs). In this study, the secretion of cytokines from peripheral blood cells and the number of peripheral blood Tregs were analyzed before and after ACT. Blood samples were collected from 109 consecutive cancer patients who received ACT, which consisted of anti-CD3 stimulated lymphokine-activated killer cells. For testing immune function, venous blood was obtained from patients before the start of therapy and after they had received 4 cycles of ACT. Of the 109 patients, 76 received ACT four times or more. All 109 blood samples at baseline and 76 follow-up samples were available. The secretion ability of various cytokines from peripheral blood cells was measured, as well as the number of peripheral blood Tregs. We found that the secretion ability of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was enhanced significantly after treatment, while the number of Tregs and the ratio of Treg to CD4 was significantly decreased. Overall survival in patients with increased IFN-γ and TNF-α secretion after ACT was significantly longer. These findings suggest a potential therapeutic role for ACT in cancer immunotherapy.

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