Tumor β‑catenin expression is associated with immune evasion in non‑small cell lung cancer with high tumor mutation burden

Muto,Satoshi; Ozaki,Yuki; Yamaguchi,Hikaru; Mine,Hayato; Takagi,Hironori; Watanabe,Masayuki; Inoue,Takuya; Yamaura,Takumi; Fukuhara,Mitsuro; Okabe,Naoyuki; Matsumura,Yuki; Hasegawa,Takeo; Osugi,Jun; Hoshino,Mika; Higuchi,Mitsunori; Shio,Yutaka; Nanamiya,Hideaki; Imai,Jun-Ichi; Isogai,Takao; Watanabe,Shinya; Suzuki,Hiroyuki

doi:10.3892/ol.2021.12464

Tumor β‑catenin expression is associated with immune evasion in non‑small cell lung cancer with high tumor mutation burden

Authors:
- Satoshi Muto
- Yuki Ozaki
- Hikaru Yamaguchi
- Hayato Mine
- Hironori Takagi
- Masayuki Watanabe
- Takuya Inoue
- Takumi Yamaura
- Mitsuro Fukuhara
- Naoyuki Okabe
- Yuki Matsumura
- Takeo Hasegawa
- Jun Osugi
- Mika Hoshino
- Mitsunori Higuchi
- Yutaka Shio
- Hideaki Nanamiya
- Jun-Ichi Imai
- Takao Isogai
- Shinya Watanabe
- Hiroyuki Suzuki
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Affiliations: Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan, Translational Research Center, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan
Published online on: January 12, 2021 https://doi.org/10.3892/ol.2021.12464
Article Number: 203
Copyright: © Muto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

β‑catenin expression by tumor cells suppressed dendritic cell recruitment to the tumor microenvironment in a melanoma model, resulting in fewer tumor‑infiltrating lymphocytes. Immunohistochemistry was used in the present study to examine the association between the expression of β‑catenin and tumor infiltrating lymphocytes and CD11c⁺ cells in 122 patients with non‑small cell lung cancer (NSCLC), who underwent radical surgery. β‑catenin was positive in 24% of NSCLC tumors compared with 59% of squamous cell carcinomas and 11% of adenocarcinomas. There was no significant association between the expression of β‑catenin and the frequency of CD8⁺ cell infiltration into tumor tissues, including the stroma. Conversely, the infiltration of CD8⁺ cells into tumor nests was significantly lower in β‑catenin‑positive cases compared with that in negative β‑catenin cases. Similarly, CD11c⁺ cell infiltration was significantly lower in the β‑catenin‑positive group. The β‑catenin‑positive group had shorter overall survival and recurrence‑free survival times compared with that in the negative group. Furthermore, β‑catenin‑positive NSCLC had a high tumor mutation burden, but tended to have a low expression of programmed death‑ligand 1. In conclusion, the expression of β‑catenin in NSCLC was negatively associated with CD11c⁺ cells and cytotoxic T cell infiltration at the tumor site and had a tendency towards a poor prognosis.

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