PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer

Michitaka Nakano, Mamoru Ito, Risa Tanaka, Kyoko Yamaguchi, hiroshi ariyama, Kenji Mitsugi, Tomoyasu Yoshihiro, Hirofumi Ohmura, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kosuke Sagara, Yuta Okumura, Kenta Nio, Kenji Tsuchihashi, Shuji Arita, Hitoshi Kusaba, Koichi Akashi, Eishi Baba

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

The liquid biopsy of ascites fluid could be an excellent source of tumor and microenvironment for the study of prognostic biomarkers because of its accessibility. Tumor-infiltrating lymphocytes (TILs) can predict prognosis in multiple malignancies, including the response to immune checkpoint inhibitors, a breakthrough cancer therapy. However, TILs’ profiles from malignant ascites have not been extensively studied. Using flow cytometric analysis, we quantified the proportion of exhausted T cells and memory/naive/effector T-cell subsets, among the CD4+ and CD8+ T-cell populations of paired TILs and peripheral blood T cell samples (n = 22). The correlation between CD4+ and CD8+ subset profiles suggested that the combined analysis of CD4+ and CD8+ cells in malignant ascites was clinically significant. We found that cells positive for the exhaustion markers programmed cell death-1 (PD-1), and T-cell immunoglobulin and mucin domain 3 (TIM-3), and cells coexpressing PD-1 and TIM-3 abundantly exist among malignant ascites TILs. Furthermore, patients with high frequency of PD-1+ TIM-3+ cells among the CD4+ and CD8+ T-cell population showed worse clinical outcome in multivariate analysis (n = 27). We propose that exhausted ascites TILs represent a clinically significant prognostic biomarker in advanced gastrointestinal cancer and represent an important target for immune checkpoint inhibitors.

元の言語英語
ページ(範囲)2986-2992
ページ数7
ジャーナルCancer Science
109
発行部数9
DOI
出版物ステータス出版済み - 9 1 2018

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Tumor-Infiltrating Lymphocytes
Gastrointestinal Neoplasms
Ascites
Cell Death
T-Lymphocytes
Mucin-3
Biomarkers
Tumor Microenvironment
T-Lymphocyte Subsets
Population
Blood Cells
Neoplasms
Multivariate Analysis
Biopsy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer. / Nakano, Michitaka; Ito, Mamoru; Tanaka, Risa; Yamaguchi, Kyoko; ariyama, hiroshi; Mitsugi, Kenji; Yoshihiro, Tomoyasu; Ohmura, Hirofumi; Tsuruta, Nobuhiro; Hanamura, Fumiyasu; Sagara, Kosuke; Okumura, Yuta; Nio, Kenta; Tsuchihashi, Kenji; Arita, Shuji; Kusaba, Hitoshi; Akashi, Koichi; Baba, Eishi.

:: Cancer Science, 巻 109, 番号 9, 01.09.2018, p. 2986-2992.

研究成果: ジャーナルへの寄稿記事

Nakano, M, Ito, M, Tanaka, R, Yamaguchi, K, ariyama, H, Mitsugi, K, Yoshihiro, T, Ohmura, H, Tsuruta, N, Hanamura, F, Sagara, K, Okumura, Y, Nio, K, Tsuchihashi, K, Arita, S, Kusaba, H, Akashi, K & Baba, E 2018, 'PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer', Cancer Science, 巻. 109, 番号 9, pp. 2986-2992. https://doi.org/10.1111/cas.13723
Nakano, Michitaka ; Ito, Mamoru ; Tanaka, Risa ; Yamaguchi, Kyoko ; ariyama, hiroshi ; Mitsugi, Kenji ; Yoshihiro, Tomoyasu ; Ohmura, Hirofumi ; Tsuruta, Nobuhiro ; Hanamura, Fumiyasu ; Sagara, Kosuke ; Okumura, Yuta ; Nio, Kenta ; Tsuchihashi, Kenji ; Arita, Shuji ; Kusaba, Hitoshi ; Akashi, Koichi ; Baba, Eishi. / PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer. :: Cancer Science. 2018 ; 巻 109, 番号 9. pp. 2986-2992.
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T1 - PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer

AU - Nakano, Michitaka

AU - Ito, Mamoru

AU - Tanaka, Risa

AU - Yamaguchi, Kyoko

AU - ariyama, hiroshi

AU - Mitsugi, Kenji

AU - Yoshihiro, Tomoyasu

AU - Ohmura, Hirofumi

AU - Tsuruta, Nobuhiro

AU - Hanamura, Fumiyasu

AU - Sagara, Kosuke

AU - Okumura, Yuta

AU - Nio, Kenta

AU - Tsuchihashi, Kenji

AU - Arita, Shuji

AU - Kusaba, Hitoshi

AU - Akashi, Koichi

AU - Baba, Eishi

PY - 2018/9/1

Y1 - 2018/9/1

N2 - The liquid biopsy of ascites fluid could be an excellent source of tumor and microenvironment for the study of prognostic biomarkers because of its accessibility. Tumor-infiltrating lymphocytes (TILs) can predict prognosis in multiple malignancies, including the response to immune checkpoint inhibitors, a breakthrough cancer therapy. However, TILs’ profiles from malignant ascites have not been extensively studied. Using flow cytometric analysis, we quantified the proportion of exhausted T cells and memory/naive/effector T-cell subsets, among the CD4+ and CD8+ T-cell populations of paired TILs and peripheral blood T cell samples (n = 22). The correlation between CD4+ and CD8+ subset profiles suggested that the combined analysis of CD4+ and CD8+ cells in malignant ascites was clinically significant. We found that cells positive for the exhaustion markers programmed cell death-1 (PD-1), and T-cell immunoglobulin and mucin domain 3 (TIM-3), and cells coexpressing PD-1 and TIM-3 abundantly exist among malignant ascites TILs. Furthermore, patients with high frequency of PD-1+ TIM-3+ cells among the CD4+ and CD8+ T-cell population showed worse clinical outcome in multivariate analysis (n = 27). We propose that exhausted ascites TILs represent a clinically significant prognostic biomarker in advanced gastrointestinal cancer and represent an important target for immune checkpoint inhibitors.

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