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Greater extent of blood-tumor TCR repertoire overlap is associated with favorable clinical responses to PD-1 blockade.
Aoki, Hiroyasu; Ueha, Satoshi; Nakamura, Yoshiaki; Shichino, Shigeyuki; Nakajima, Hiromichi; Shimomura, Manami; Sato, Akihiro; Nakatsura, Tetsuya; Yoshino, Takayuki; Matsushima, Kouji.
Afiliación
  • Aoki H; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda City, Japan.
  • Ueha S; Department of Hygiene, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Nakamura Y; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda City, Japan.
  • Shichino S; Translational Research Support Section, National Cancer Center Hospital East, Kashiwa City, Japan.
  • Nakajima H; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa City, Japan.
  • Shimomura M; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda City, Japan.
  • Sato A; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa City, Japan.
  • Nakatsura T; Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Kashiwa, Japan.
  • Yoshino T; Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Kashiwa, Japan.
  • Matsushima K; Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa City, Japan.
Cancer Sci ; 112(8): 2993-3004, 2021 Aug.
Article en En | MEDLINE | ID: mdl-34014607
With the widespread use of programmed death receptor-1 (PD-1) blockade therapy, sensitive and specific predictive biomarkers that guide patient selection are urgently needed. T-cell receptor (TCR) repertoire, which reflects antitumor T-cell responses based on antigen specificity, is expected as a novel biomarker for PD-1 blockade therapy. In the present study, the TCR repertoire of eight patients with gastrointestinal cancer treated with anti-PD-1 antibody (nivolumab) was analyzed. To analyze the tumor-associated T-cell clones in the blood and their mobilization into the tumor, we focused on T-cell clones that presented in both blood and tumor (blood-tumor overlapping clones). Responders to PD-1 blockade tended to exhibit a higher number of overlapping clones in the tumor and a higher total frequency in the blood. Moreover, a higher total frequency of overlapping clones in blood CD8+ T cells before treatment was associated with a favorable clinical response. Collectively, these results suggest the possibility of blood-tumor TCR repertoire overlap to predict clinical response to PD-1 blockade and guide patient selection before the treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Análisis de Secuencia de ADN / Nivolumab / Neoplasias Gastrointestinales / Inhibidores de Puntos de Control Inmunológico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Sci Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Análisis de Secuencia de ADN / Nivolumab / Neoplasias Gastrointestinales / Inhibidores de Puntos de Control Inmunológico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Sci Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido