Immunogenomic landscape of gynecologic carcinosarcoma

• Project/Area Number: 18K07338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Mori Seiichi 公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, プロジェクトリーダー (10334814)
• Co-Investigator(Kenkyū-buntansha): 清谷 一馬 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 主任研究員 (30433642)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 婦人科癌肉腫 / ゲノム情報 / 免疫微小環境 / T細胞受容体レパトワ / 免疫ゲノム / がん肉腫 / TCRレパトワ / 免疫細胞プロファイリング / 癌肉腫 / ハイパーミューテーター / 腫瘍免疫 / レパトワ解析

Outline of Final Research Achievements

Gynecological carcinosarcoma (CS) is a rare, biphasic tumor comprising epithelial and mesenchymal elements, and exhibits more aggressive clinical features. Four molecular subtypes of CS were recently established (POLE, MSI, CNH, and CNL) and shown to be associated with multiple clinicopathological parameters. However, the role of the immune microenvironment in CS remains unclear. Relying on estimations of tumor-infiltrating cell types from RNA-seq data, POLE and MSI tumors showed an enrichment of M1 macrophages, plasma cells and CD8+ T cells, whereas CNH and CNL tumors had high levels of M2 macrophages. T-cell heterogeneity was independently correlated with prolonged progression-free survival. Differential analysis of carcinoma and sarcoma elements identified many shared mutations but there was little overlap in the T-cell receptor repertoire between the two elements.

Academic Significance and Societal Importance of the Research Achievements

非常に予後の悪い、婦人科癌肉腫がなぜ予後が悪いのか、マルチオミックス情報を取得して、免疫微小環境について検索した。我々の研究により、再発しやすい癌肉腫と再発しにくい癌肉腫の免疫学的な特徴を明らかにした。我々の研究は、一部の癌肉腫に対して有効な治療法を見つけることに貢献できるものと考える。

Research Products

• [Journal Article] Immunogenomic landscape of gynecologic carcinosarcoma (2021)
  • Author(s): Gotoh Osamu、Kiyotani Kazuma、Chiba Tomohiro、Sugiyama Yuko、Takazawa Yutaka、Nemoto Kensaku、Kato Kazuyoshi、Tanaka Norio、Nomura Hidetaka、Hasegawa Kosei、Fujiwara Keiichi、Takamatsu Shiro、Matsumura Noriomi、Noda Tetsuo、Mori Seiichi
  • Journal Title: Gynecologic Oncology Volume: 160 Issue: 2 Pages: 547-556
  • DOI: 10.1016/j.ygyno.2020.11.030
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenicity assessment of variants for breast cancer susceptibility genes based on BRCAness of tumor sample (2021)
  • Author(s): Yoshida R, Hagio T, Kaneyasu T, Gotoh O, Osako T, Tanaka N, Amino S, Yaguchi N, Nakashima E, Kitagawa D, Ueno T, Ohno S, Nakajima T, Nakamura S, Miki Y, Hirota T, Takahashi S, Matsuura M, Noda T, Mori S.
  • Journal Title: Cancer Sci. Volume: 112(3) Issue: 3 Pages: 1310-1319
  • DOI: 10.1111/cas.14803
  • Peer Reviewed / Open Access
• [Journal Article] T-cell complexity and density are associated with sensitivity to neoadjuvant chemoradiotherapy in patients with rectal cancer (2020)
  • Author(s): Akiyoshi T, Gotoh O, Tanaka N, Kiyotani K, Yamamoto N, Ueno M, Fukunaga Y, Mori S.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 70 Issue: 2 Pages: 509-518
  • DOI: 10.1007/s00262-020-02705-6
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome (2020)
  • Author(s): Kaneyasu T, Mori S, Yamauchi H, et al.
  • Journal Title: NPJ Breast Cancer. Volume: 6 Issue: 1 Pages: 25-25
  • DOI: 10.1038/s41523-020-0163-1
  • Peer Reviewed / Open Access
• [Journal Article] Sequencing artifacts derived from a library preparation method using enzymatic fragmentation. (2020)
  • Author(s): Tanaka N, Takahara A, Hagio T, Nishiko R, Kanayama J, Gotoh O, Mori S.
  • Journal Title: PLoS One. Volume: 15 Issue: 1 Pages: 427-427
  • DOI: 10.1371/journal.pone.0227427
  • Peer Reviewed / Open Access
• [Journal Article] Two Distinct Tumorigenic Processes in Endometrial Endometrioid Adenocarcinoma. (2020)
  • Author(s): Sugiyama Y, Gotoh O, Fukui N, Tanaka N, Hasumi K, Takazawa Y, Noda T, Mori S.
  • Journal Title: Am J Pathol. Volume: 190 Issue: 1 Pages: 234-234
  • DOI: 10.1016/j.ajpath.2019.09.022
  • Peer Reviewed
• [Journal Article] Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma. (2019)
  • Author(s): Gotoh O, Sugiyama Y, Takazawa Y, Kato K, Tanaka N, Omatsu K, Takeshima N, Nomura H, Hasegawa K, Fujiwara K, Taki M, Matsumura N, Noda T, Mori S.
  • Journal Title: Nat Commun. Volume: 10 Issue: 1 Pages: 4965-4965
  • DOI: 10.1038/s41467-019-12985-x
  • Peer Reviewed / Open Access
• [Journal Article] Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer (2018)
  • Author(s): Ogura Atsushi、Akiyoshi Takashi、Yamamoto Noriko、Kawachi Hiroshi、Ishikawa Yuichi、Mori Seiichi、Oba Koji、Nagino Masato、Fukunaga Yosuke、Ueno Masashi
  • Journal Title: European Journal of Cancer Volume: 91 Pages: 11-20
  • DOI: 10.1016/j.ejca.2017.12.005
  • Peer Reviewed / Open Access
• [Journal Article] TP53 and OSBPL10 alterations in diffuse large B-cell lymphoma: prognostic markers identified via exome analysis of cases with extreme prognosis. (2018)
  • Author(s): Dobashi A, Togashi Y, Tanaka N, Yokoyama M, Tsuyama N, Baba S, Mori S, Hatake K, Yamaguchi T, Noda T, Takeuchi K.
  • Journal Title: Oncotarget Volume: 9 Issue: 28 Pages: 19555-19568
  • DOI: 10.18632/oncotarget.24656
  • Peer Reviewed / Open Access
• [Journal Article] Ethical concerns on sharing genomic data including patients' family members. (2018)
  • Author(s): Takashima K, Maru Y, Mori S, Mano H, Noda T, Muto K.
  • Journal Title: BMC Med Ethics. Volume: 19 Issue: 1 Pages: 61-61
  • DOI: 10.1186/s12910-018-0310-5
  • Peer Reviewed / Open Access