{"id":"hum0294","secondaryIds":[],"version":2,"url":"https://humandbs.dbcls.jp/research/hum0294/v2","datePublished":"2026-11-02","versions":[{"version":1,"datePublished":"2024-05-29"},{"version":2,"datePublished":"2026-11-02"}],"title":{"ja":"腫瘍浸潤T細胞サブセットのシングルセル解析","en":"Single cell analysis of tumor-infiltrating T cells"},"summary":{"aims":{"ja":"｢切除不能局所進行食道扁平上皮癌を対象とした化学放射線療法後の逐次治療としてのアテゾリズマブ単独療法の安全性及び有効性を検討する多施設共同第Ⅱ相臨床相試験｣に付随するバイオマーカーの探索研究（通称：TENERGY-TR）に参加した食道がん患者の治療前の腫瘍と正常細胞のwhole exome sequencing（WES）解析と、治療前、放射線化学療法後、アテゾリズマブ投与後の3点の腫瘍生検検体のRNA-seq解析を実施し、治療効果予測バイオマーカー探索につなげること。\n「切除不能進行・再発胃/食道胃接合部/食道腺癌患者を対象としたRegorafenib と Nivolumab 及び化学療法の同時併用療法の第 Ib/II 相臨床試験（通称：REGONIVOCTx）」に参加した胃がん・食道胃接合部がん患者を対象に、治療前、治療中および病勢増悪時に採取した腫瘍検体のscRNA-seqおよびscTCR-seq解析を行う。これにより、治療に伴う腫瘍微小環境の経時的変化を捉え、治療効果を予測するバイオマーカーの同定および治療耐性機序の解明を目指す。","en":"The objective is to analyze tumor and normal cell whole exome sequencing (WES) of esophageal cancer patients participating in the TENERGY-TR before treatment and RNA-seq specimens of tumor biopsy specimens at three points before treatment, after radiation chemotherapy, and after Atezolizumab administration, to search for biomarkers to predict treatment response.\nThe objective is to perform single-cell RNA sequencing (scRNA-seq) and single-cell T-cell receptor sequencing (scTCR-seq) of tumor samples collected before treatment, during treatment, and at disease progression from patients with gastric or gastroesophageal junction cancer participating in “A Phase Ib/II study of regorafenib and nivolumab plus chemotherapy in patients with unresectable advanced/recurrent gastric/gastroesophageal junction/esophageal adenocarcinoma” (REGONIVOCTx). These analyses aim to characterize longitudinal changes in the tumor microenvironment during treatment, identify biomarkers predictive of treatment response, and elucidate mechanisms of treatment resistance."},"methods":{"ja":"各時点で取得した凍結腫瘍サンプルまたは血液サンプルを対象に、AllPrep DNA/RNA Mini kit（Qiagen）を用いてDNA/RNAを抽出し、WESならびにRNA-seq解析を実施した。\n10x Genomics Chromium Single Cell 5′ v2キットを用いてライブラリを構築し、scRNA-seqとscTCR-seq解析を実施した。","en":"DNA/RNA was extracted from frozen tumor or blood samples using an AllPrep DNA/RNA Mini kit (Qiagen) at each time point. Whole exome sequencing and RNA sequencing analyses were performed.\nChromium Single Cell 5' Reagent Kit v2 (10x Genomics) was used to generate scRNA-seq and scTCR-seq libraries and sequenced on an Illumina NovaSeq 6000."},"targets":{"ja":"TENERGY-TRに参加した食道がん28症例。\n- WES：治療前の腫瘍組織（27検体）と正常組織（27検体）のペア、\n- RNA-seq：治療前（28検体）、放射線化学療法後（25検体）、アテゾリズマブ投与後（25検体）の3点の腫瘍生検検体\nREGONIVOCTx試験（EPOC2104）に登録された切除不能進行・再発胃がんまたは食道胃接合部がん14症例（胃がん12、食道胃接合部がん2）\n- scRNA-seq/scTCR-seq：治療前（14検体：胃がん12、食道胃接合部がん2）、治療中（12検体：胃がん10、食道胃接合部がん2）、および増悪時（9検体：胃がん7、食道胃接合部がん2）の腫瘍検体","en":"esophageal cancer patients participating in the Tenergy trial\n- WES: tumor tissue (27 samples) and normal tissue (27 samples) from esophageal cancer patients\n- RNA-seq: tumor biopsy specimens at three-time points before treatment (28 samples), after radiation chemotherapy (25 samples) and after Atezolizumab administration (25 samples)\nadvanced gastric or gastroesophageal junction (GEJ) cancer patients participating in the REGONIVOCTx trial (EPOC2104)\n- scRNA-seq/scTCR-seq: tumor specimens from 14 patients with advanced gastric or GEJ cancer at three time points (12 gastric, 2 GEJ): before treatment (14 samples: 12 gastric, 2 GEJ), during treatment (12 samples: 10 gastric, 2 GEJ), and at disease progression (9 samples: 7 gastric, 2 GEJ)"},"url":{"ja":[{"url":"https://doi.org/10.1186/s12885-020-06716-5","text":"https://doi.org/10.1186/s12885-020-06716-5"}],"en":[{"url":"https://doi.org/10.1186/s12885-020-06716-5","text":"https://doi.org/10.1186/s12885-020-06716-5"}]}},"listingSummary":{"methods":{"ja":"配列決定\n発現","en":"Sequencing, Expression profiling"},"targets":{"ja":"食道癌：28症例\n胃癌：12例\n食道胃接合部癌：2例\n（日本人）","en":"esophageal cancer: 28 cases\ngastric cancer: 12 cases\ngastroesophageal junction cancer: 2 cases\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Exome、RNA-seq、scRNA-seq、scTCR-seq）","en":"NGS\n(Exome, RNA-seq, scRNA-seq, scTCR-seq)"}},"releaseNote":{"ja":"切除不能進行・再発胃がんまたは食道胃接合部がん14症例から採取した腫瘍組織を単一細胞に解離し、scRNA-seq/scTCR-seqを実施して得られたシーケンスデータをfastq形式で提供する。","en":"Tumor tissues collected from 14 patients with unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) cancer were dissociated into single cells and subjected to scRNA-seq/scTCR-seq analysis. Fastq files are provided."},"dataProviders":[{"name":{"ja":"熊谷 尚悟","en":"Shogo Kumagai"},"organization":{"name":{"ja":"国立がん研究センター 先端医療開発センター 免疫トランスレーショナルリサーチ分野","en":"Division of Cancer Immunology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center"}}},{"name":{"ja":"板橋 耕太","en":"Kota Itahashi"},"organization":{"name":{"ja":"国立がん研究センター 先端医療開発センター 免疫トランスレーショナルリサーチ分野","en":"Division of Cancer Immunology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center"}}}],"researchProjects":[{"name":{"ja":null,"en":null},"url":{"ja":[{"url":"https://jrct.mhlw.go.jp/latest-detail/jRCT2031220089","text":"https://jrct.mhlw.go.jp/latest-detail/jRCT2031220089"}],"en":[{"url":"https://jrct.mhlw.go.jp/en-latest-detail/jRCT2031220089","text":"https://jrct.mhlw.go.jp/en-latest-detail/jRCT2031220089"}]}}],"grants":[{"title":{"ja":"切除不能局所進行食道扁平癌を対象とした化学放射線療法後の逐次治療としての抗PD-1抗体薬療法の安全性・有効性・proof-of-concept (POC)を検討する多施設共同臨床第Ib/II相試験","en":"A phase II, multicenter study to investigate the safety, efficacy, and proof-of-concept (POC) of Anti PD-L1 antibody monotherapy following radical chemoradiotherapy in patients with inoperable locally advanced esophageal squamous cell cancer"},"agency":{"ja":"日本医療研究開発機構（AMED） 革新的がん医療実用化研究事業","en":"Practical Research for Innovative Cancer Control, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP21ck0106420"]}],"relatedPublications":[{"title":"Atezolizumab following definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma – a multicenter phase 2 trial (EPOC1802)","doi":"https://doi.org/10.1038/s43018-025-00918-1","datasets":["JGAD000841"]},{"title":"Longitudinal remodeling of the tumor-immune microenvironment during regorafenib, nivolumab, and chemotherapy in advanced gastric cancer","datasets":["JGAD001127"]}],"datasets":["JGAD000841","JGAD001127"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"浜田 道昭","en":"Michiaki Hamada"},"affiliation":{"ja":"浜田研究室, 理工学術院, 早稲田大学","en":"Hamada Laboratory, Faculty of Science and Engineering, Waseda University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"RNA標的創薬データベースの構築","en":"Construction of RNA-targeted Drug Discovery Database"},"periodStart":"2023-01-05","periodEnd":"2027-10-31","datasets":["JGAD000841"]}]}