Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy

Takashi Kanemura, Hiroshi Miyata, Tomoki Makino, Koji Tanaka, Keijiro Sugimura, Mika Hamada-Uematsu, Yu Mizote, Hiroaki Uchida, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Hisashi Wada, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Hideaki Tahara

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Abstract

Milk fat globule-epidermal growth factor factor 8 (MFG-E8) is secreted from macrophages and is known to induce immunological tolerance mediated by regulatory T cells. However, the roles of the MFG-E8 that is expressed by cancer cells have not yet been fully examined. Expression of MFG-E8 was examined using immunohistochemistry in surgical samples from 134 patients with esophageal squamous cell carcinoma. The relationships between MFG-E8 expression levels and clinicopathological factors, including tumor-infiltrating lymphocytes, were evaluated. High MFG-E8 expression was observed in 23.9% of the patients. The patients with tumors highly expressing MFG-E8 had a significantly higher percentage of neoadjuvant chemotherapy (NAC) history (P <.0001) and shorter relapse-free survival (P = 0.012) and overall survival (OS; P =.0047). On subgroup analysis, according to NAC history, patients with high MFG-E8 expression had significantly shorter relapse-free survival (P =.027) and OS (P =.0039) only when they had been treated with NAC. Furthermore, tumors with high MFG-E8 expression had a significantly lower ratio of CD8+ T cells/regulatory T cells in tumor-infiltrating lymphocytes (P =.042) only in the patients treated with NAC, and those with a lower ratio had a shorter OS (P =.026). High MFG-E8 expression was also found to be an independent prognostic factor in multivariate analysis. The abundant MFG-E8 expression in esophageal squamous cell carcinoma might have a negative influence on the long-term survival of patients after chemotherapy by affecting T-cell regulation in the tumor microenvironment.

Original languageEnglish
Pages (from-to)3393-3402
Number of pages10
JournalCancer Science
Volume109
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

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Esophageal Neoplasms
Epidermal Growth Factor
Drug Therapy
Tumor-Infiltrating Lymphocytes
Survival
Regulatory T-Lymphocytes
History
milk fat globule
T-Lymphocytes
Recurrence
Neoplasms
Tumor Microenvironment
Multivariate Analysis
Immunohistochemistry
Macrophages

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kanemura, T., Miyata, H., Makino, T., Tanaka, K., Sugimura, K., Hamada-Uematsu, M., ... Tahara, H. (2018). Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy. Cancer Science, 109(11), 3393-3402. https://doi.org/10.1111/cas.13785

Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy. / Kanemura, Takashi; Miyata, Hiroshi; Makino, Tomoki; Tanaka, Koji; Sugimura, Keijiro; Hamada-Uematsu, Mika; Mizote, Yu; Uchida, Hiroaki; Miyazaki, Yasuhiro; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Wada, Hisashi; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro; Tahara, Hideaki.

In: Cancer Science, Vol. 109, No. 11, 01.11.2018, p. 3393-3402.

Research output: Contribution to journalArticle

Kanemura, T, Miyata, H, Makino, T, Tanaka, K, Sugimura, K, Hamada-Uematsu, M, Mizote, Y, Uchida, H, Miyazaki, Y, Takahashi, T, Kurokawa, Y, Yamasaki, M, Wada, H, Nakajima, K, Takiguchi, S, Mori, M, Doki, Y & Tahara, H 2018, 'Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy', Cancer Science, vol. 109, no. 11, pp. 3393-3402. https://doi.org/10.1111/cas.13785
Kanemura T, Miyata H, Makino T, Tanaka K, Sugimura K, Hamada-Uematsu M et al. Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy. Cancer Science. 2018 Nov 1;109(11):3393-3402. https://doi.org/10.1111/cas.13785
Kanemura, Takashi ; Miyata, Hiroshi ; Makino, Tomoki ; Tanaka, Koji ; Sugimura, Keijiro ; Hamada-Uematsu, Mika ; Mizote, Yu ; Uchida, Hiroaki ; Miyazaki, Yasuhiro ; Takahashi, Tsuyoshi ; Kurokawa, Yukinori ; Yamasaki, Makoto ; Wada, Hisashi ; Nakajima, Kiyokazu ; Takiguchi, Shuji ; Mori, Masaki ; Doki, Yuichiro ; Tahara, Hideaki. / Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy. In: Cancer Science. 2018 ; Vol. 109, No. 11. pp. 3393-3402.
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AU - Sugimura, Keijiro

AU - Hamada-Uematsu, Mika

AU - Mizote, Yu

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AU - Mori, Masaki

AU - Doki, Yuichiro

AU - Tahara, Hideaki

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