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Immune microenvironment in Barrett’s esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression

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Abstract

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett’s esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia–adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

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Abbreviations

BE:

Barrett’s esophagus

EAC:

esophageal adenocarcinoma

EGJ:

esophagogastric junction

ESD:

endoscopic submucosal dissection

LPL:

lamina propria lymphocyte

LSBE:

long-segment BE

SSBE:

short-segment BE

TIL:

tumor-infiltrating lymphocyte

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Acknowledgments

We would like to acknowledge Ms. Yayoi Aoyama and Ms. Yasuko Furukawa for technical support.

Author information

Authors and Affiliations

  1. Department of Surgery, Tohoku University Hospital, Sendai, Japan

    Yusuke Gokon, Yusuke Taniyama, Hirotaka Ishida & Takashi Kamei

  2. Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Yusuke Gokon, Fumiyoshi Fujishima & Hironobu Sasano

  3. Department of Gastroenterology, Sendai City Medical Center, Sendai, Japan

    Taku Yamagata

  4. Department of Pathology, Sendai City Medical Center, Sendai, Japan

    Takashi Sawai

  5. Department of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Japan

    Miwa Uzuki

  6. Department of Surgery, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan

    Hirofumi Ichikawa

  7. Department of Pathology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan

    Yuko Itakura

  8. Department of Surgery, Hachinohe City Hospital, Hachinohe, Japan

    Kazutomi Takahashi

  9. Department of Pathology and Laboratory Medicine, Hachinohe City Hospital, Hachinohe, Japan

    Nobuhisa Yajima

  10. Department of Surgery, Nihonkai General Hospital, Sakata, Japan

    Motohisa Hagiwara

  11. Department of Pathology, Nihonkai General Hospital, Sakata, Japan

    Akiko Nishida

  12. Department of Gastrointestinal Surgery, Iwate Prefectural Central Hospital, Morioka, Japan

    Yohei Ozawa

  13. Department of Pathology, Iwate Prefectural Central Hospital, Morioka, Japan

    Tsutomu Sakuma

  14. Department of Surgery, Osaki Citizen Hospital, Ōsaki, Japan

    Rikiya Kanba

  15. Department of Pathology, Osaki Citizen Hospital, Ōsaki, Japan

    Kazuhiro Sakamoto

  16. Department of Surgery, Hiraka General Hospital, Yokote, Japan

    Masashi Zuguchi

  17. Department of Pathology, Hiraka General Hospital, Yokote, Japan

    Masahiro Saito

Authors
  1. Yusuke Gokon
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  2. Fumiyoshi Fujishima
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  8. Hirofumi Ichikawa
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  21. Hironobu Sasano
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Yusuke Gokon, Fumiyoshi Fujishima, Hirotaka Ishida, Taku Yamagata, Takashi Sawai, Miwa Uzuki, Hirofumi Ichikawa, Yuko Itakura, Kazutomi Takahashi, Nobuhisa Yajima, Motohisa Hagiwara, Akiko Nishida, Yohei Ozawa, Tsutomu Sakuma, Rikiya Kanba, Kazuhiro Sakamoto, Masashi Zuguchi, and Masahiro Saito. The first draft of the manuscript was written by Yusuke Gokon and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fumiyoshi Fujishima.

Ethics declarations

The study protocol was approved by the ethics committee or institutional review board of each participating institution (Accession number of Tohoku University Hospital 2017–1-325). Informed consent was obtained for experimentation with human subjects.

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The authors declare that they have no conflict of interest.

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Gokon, Y., Fujishima, F., Taniyama, Y. et al. Immune microenvironment in Barrett’s esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression. Virchows Arch 477, 825–834 (2020). https://doi.org/10.1007/s00428-020-02854-0

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