Open AccessPD ‐1+ TIM ‐3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer
Author(s) -
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
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13723
Subject(s) - ascites , cancer , medicine , gastrointestinal cancer , cancer research , gastroenterology , colorectal cancer
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 ( TIL s) can predict prognosis in multiple malignancies, including the response to immune checkpoint inhibitors, a breakthrough cancer therapy. However, TIL s’ 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 CD 4+ and CD 8+ T‐cell populations of paired TIL s and peripheral blood T cell samples (n = 22). The correlation between CD 4+ and CD 8+ subset profiles suggested that the combined analysis of CD 4+ and CD 8+ 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 TIL s. Furthermore, patients with high frequency of PD ‐1+ TIM ‐3+ cells among the CD 4+ and CD 8+ T‐cell population showed worse clinical outcome in multivariate analysis (n = 27). We propose that exhausted ascites TIL s represent a clinically significant prognostic biomarker in advanced gastrointestinal cancer and represent an important target for immune checkpoint inhibitors.