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Cancer Immunology Research
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Research Article

Pretreatment immune status correlates with progression-free survival in chemotherapy-treated metastatic colorectal cancer patients

Kohei Tada, Shigehisa Kitano, Hirokazu Shoji, Takashi Nishimura, Yasuhiro Shimada, Kengo Nagashima, Kazunori Aoki, Nobuyoshi Hiraoka, Yoshitaka Honma, Satoru Iwasa, Natsuko Okita, Atsuo Takashima, Ken Kato, Yasuhide Yamada, Naoyuki Katayama, Narikazu Boku, Yuji Heike and Tetsuya Hamaguchi
Kohei Tada
1Immunotherapy and Cell Therapy Service, St. Luke's International Hospital
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Shigehisa Kitano
2Experimental Therapeutics, National Cancer Center Hospital
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Hirokazu Shoji
3Gastorointestinal Medical Oncology Division, National Cancer Center Hospital
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Takashi Nishimura
4Department of Gastrointestinal Medicine, Tokyo Jikei Medical University
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Yasuhiro Shimada
5Gastrointestinal Medical Oncology Division, National Cancer Center Hospital
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Kengo Nagashima
6Department of Global Clinical Research, Chiba University Graduate School of Medicine
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Kazunori Aoki
7Division of Molecular and Cellular Medicine, National Cancer Center Research Institute
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Nobuyoshi Hiraoka
8Division of Molecular Pathology, National Cancer Center Research Institute
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Yoshitaka Honma
3Gastorointestinal Medical Oncology Division, National Cancer Center Hospital
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Satoru Iwasa
3Gastorointestinal Medical Oncology Division, National Cancer Center Hospital
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Natsuko Okita
5Gastrointestinal Medical Oncology Division, National Cancer Center Hospital
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Atsuo Takashima
5Gastrointestinal Medical Oncology Division, National Cancer Center Hospital
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Ken Kato
5Gastrointestinal Medical Oncology Division, National Cancer Center Hospital
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Yasuhide Yamada
5Gastrointestinal Medical Oncology Division, National Cancer Center Hospital
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Naoyuki Katayama
9Department of Hematology and Oncology, Mie University Graduate School of Medicine
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Narikazu Boku
10Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital
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Yuji Heike
1Immunotherapy and Cell Therapy Service, St. Luke's International Hospital
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  • For correspondence: heiyuji@luke.ac.jp
Tetsuya Hamaguchi
5Gastrointestinal Medical Oncology Division, National Cancer Center Hospital
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DOI: 10.1158/2326-6066.CIR-15-0298
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Abstract

It remains unclear whether the immunological status of cells in peripheral blood can be used as a prognostic indicator of predicts response to treatment for patients with unresectable metastatic colorectal cancer (MCRC). We therefore investigated the relationship between the pretreatment immunological status of 40 MCRC patients who planned to receive the first-line chemotherapy and their progression-free survival. Twenty-five immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSC) and effector memory T cells (TEM), were measured by multicolor-flow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared progression-free survival of the two groups. Patients with high M-MDSC, low CD4+ TEM, or low CD8+ TEM quantities had significantly shorter progression-free survival (P = 0.004, 0.005, and 0.002, respectively). Patients were classified into two prognostic groups based on numbers of adverse factors; having two or three adverse factors (n = 21, 52.5%) correlated with significantly shorter progression-free survival compared to none or 1 (n = 19, 47.5%) (P < 0.001). The presence of two or three adverse factors was an independent poor prognostic factor for progression-free survival (HR, 9.2; 95% CI, 2.5-34.2; P < 0.001). These results provide evidence that pretreatment peripheral immune status can inform the outcome of MCRC patients treated with first-line chemotherapy.

  • Received December 8, 2015.
  • Revision received March 2, 2016.
  • Accepted March 18, 2016.
  • Copyright ©2016, American Association for Cancer Research.
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This OnlineFirst version was published on April 28, 2016
doi: 10.1158/2326-6066.CIR-15-0298

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Pretreatment immune status correlates with progression-free survival in chemotherapy-treated metastatic colorectal cancer patients
Kohei Tada, Shigehisa Kitano, Hirokazu Shoji, Takashi Nishimura, Yasuhiro Shimada, Kengo Nagashima, Kazunori Aoki, Nobuyoshi Hiraoka, Yoshitaka Honma, Satoru Iwasa, Natsuko Okita, Atsuo Takashima, Ken Kato, Yasuhide Yamada, Naoyuki Katayama, Narikazu Boku, Yuji Heike and Tetsuya Hamaguchi
Cancer Immunol Res April 28 2016 DOI: 10.1158/2326-6066.CIR-15-0298

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Pretreatment immune status correlates with progression-free survival in chemotherapy-treated metastatic colorectal cancer patients
Kohei Tada, Shigehisa Kitano, Hirokazu Shoji, Takashi Nishimura, Yasuhiro Shimada, Kengo Nagashima, Kazunori Aoki, Nobuyoshi Hiraoka, Yoshitaka Honma, Satoru Iwasa, Natsuko Okita, Atsuo Takashima, Ken Kato, Yasuhide Yamada, Naoyuki Katayama, Narikazu Boku, Yuji Heike and Tetsuya Hamaguchi
Cancer Immunol Res April 28 2016 DOI: 10.1158/2326-6066.CIR-15-0298
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