TY - JOUR
T1 - Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer
AU - Yamaguchi, Kyoko
AU - Ito, Mamoru
AU - Ohmura, Hirofumi
AU - Hanamura, Fumiyasu
AU - Nakano, Michitaka
AU - Tsuchihashi, Kenji
AU - Nagai, Shuntaro
AU - Ariyama, Hiroshi
AU - Kusaba, Hitoshi
AU - Yamamoto, Hidetaka
AU - Oda, Yoshinao
AU - Nakamura, Masafumi
AU - Akashi, Koichi
AU - Baba, Eishi
N1 - Funding Information:
This work was supported by the Grant-in-Aid for Scientific Research [KAKENHI Grant Numbers JP15571042, JP16747244]; Grant-in-Aid for Japan Agency for Medical Research and Development [AMED Grant Number JP16770576]. The authors thank N. Torada from Department of Surgery and Oncology, Kyushu University, for collecting CRC samples.
Publisher Copyright:
© 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient’s prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition.
AB - Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient’s prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition.
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U2 - 10.1080/2162402X.2020.1724763
DO - 10.1080/2162402X.2020.1724763
M3 - Article
C2 - 32117589
AN - SCOPUS:85079725837
VL - 9
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 1
M1 - 1724763
ER -