論文

査読有り 筆頭著者 国際誌
2019年4月

T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
  • Shiho Asaka
  • ,
  • Ting-Tai Yen
  • ,
  • Tian-Li Wang
  • ,
  • Ie-Ming Shih
  • ,
  • Stephanie Gaillard

32
4
開始ページ
576
終了ページ
584
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41379-018-0172-x

Mismatch repair-deficient endometrial cancers have a high somatic mutation burden, suggesting that patients with these tumors may benefit from immunotherapy. Elucidating the immune suppressive mechanisms of mismatch repair-deficient endometrial cancers is fundamental to developing future immune-based interventions. This study aimed to determine the immune cell populations associated with mismatch repair-deficient endometrial cancers, especially focusing on targetable regulatory pathways of the immune response. A total of 76 endometrial cancer hysterectomy specimens were evaluated for tumor-infiltrating immune cells by immunohistochemistry. Immune specific markers were used to evaluate each specimen for the number of CD8 + cytotoxic T lymphocytes, forkhead-box P3 (FoxP3) + regulatory T cells, CD68 + tumor-associated macrophages, as well as programmed death-1 (PD-1) + immune cells, and the percentage of programmed death ligand-1 (PD-L1) + immune cells. Mismatch repair-deficient tumors exhibited a significantly higher number of CD8 + cytotoxic T lymphocytes (p = 0.0006), FoxP3 + regulatory T cells (p = 0.0003), PD-1 + immune cells (p = 0.0069), and a higher percentage of PD-L1 + immune cells (p = 0.0007) occupying the tumor compared to mismatch repair-proficient endometrial cancers. There was no significant difference in CD68 + tumor-associated macrophages infiltration between the two groups. Endometrial cancers with tumor PD-L1 expression also showed significantly increased infiltration of CD8 + cytotoxic T lymphocytes (p = 0.0002), FoxP3 + regulatory T cells (p = 0.0003), PD-1 + immune cells (p < 0.0001), and PD-L1 + immune cells (p < 0.0001). Endometrial cancers showing mismatch repair-deficiency and PD-L1 expression in tumor cells exhibit a prominent T cell-inflamed phenotype. More importantly, the increased number of FoxP3 + regulatory T cells in mismatch repair-deficient endometrial cancers suggests that combination therapy by targeting both regulatory T cells and immune checkpoints may be warranted to improve clinical efficacy.

リンク情報
DOI
https://doi.org/10.1038/s41379-018-0172-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30401949
URL
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=MEDLINE&KeyUT=MEDLINE:30401949&KeyUID=MEDLINE:30401949
ID情報
  • DOI : 10.1038/s41379-018-0172-x
  • ORCIDのPut Code : 50664269
  • PubMed ID : 30401949

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