論文

査読有り 国際誌
2020年3月2日

XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary.

Oncogene
  • Ryo Tamura
  • Kosuke Yoshihara
  • Hirofumi Nakaoka
  • Nozomi Yachida
  • Manako Yamaguchi
  • Kazuaki Suda
  • Tatsuya Ishiguro
  • Koji Nishino
  • Hiroshi Ichikawa
  • Keiichi Homma
  • Akira Kikuchi
  • Yutaka Ueda
  • Yuji Takei
  • Hiroyuki Fujiwara
  • Teiichi Motoyama
  • Shujiro Okuda
  • Toshifumi Wakai
  • Ituro Inoue
  • Takayuki Enomoto
  • 全て表示

39
17
開始ページ
3541
終了ページ
3554
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41388-020-1237-0

Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.

リンク情報
DOI
https://doi.org/10.1038/s41388-020-1237-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32115573
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176584
ID情報
  • DOI : 10.1038/s41388-020-1237-0
  • PubMed ID : 32115573
  • PubMed Central 記事ID : PMC7176584

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