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Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells

Author

Listed:
  • Eishiro Mizukoshi

    (Kanazawa University)

  • Hidetoshi Nakagawa

    (Kanazawa University)

  • Toshikatsu Tamai

    (Kanazawa University)

  • Masaaki Kitahara

    (Kanazawa University)

  • Kazumi Fushimi

    (Kanazawa University)

  • Kouki Nio

    (Kanazawa University)

  • Takeshi Terashima

    (Kanazawa University)

  • Noriho Iida

    (Kanazawa University)

  • Kuniaki Arai

    (Kanazawa University)

  • Tatsuya Yamashita

    (Kanazawa University)

  • Taro Yamashita

    (Kanazawa University)

  • Yoshio Sakai

    (Kanazawa University)

  • Masao Honda

    (Kanazawa University)

  • Shuichi Kaneko

    (Kanazawa University)

Abstract

The behaviors and fates of immune cells in cancer patients, such as dysfunction and stem-like states leading to memory formation in T cells, are in intense focus of investigation. Here we show, by post hoc analysis of peripheral blood lymphocytes of hepatocellular carcinoma patients previously undergoing vaccination with tumour-associated antigen-derived peptides in our clinical trials (registration numbers UMIN000003511, UMIN000004540, UMIN000005677, UMIN000003514 and UMIN000005678), that induced peptide-specific T cell responses may persist beyond 10 years following vaccination. Tracking TCR clonotypes at the single cell level reveals in two patients that peptide-specific long-lasting CD8+ T cells acquire an effector memory phenotype that associates with cell cycle-related genes (CCNA2 and CDK1), and are characterized by high expression of IL7R, SELL, and NOSIP along with a later stage promotion of the AP-1 transcription factor network (5 years or more past vaccination). We conclude that effective anti-tumor immunity is governed by potentially proliferative memory T cells, specific to cancer antigens.

Suggested Citation

  • Eishiro Mizukoshi & Hidetoshi Nakagawa & Toshikatsu Tamai & Masaaki Kitahara & Kazumi Fushimi & Kouki Nio & Takeshi Terashima & Noriho Iida & Kuniaki Arai & Tatsuya Yamashita & Taro Yamashita & Yoshio, 2022. "Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30861-z
    DOI: 10.1038/s41467-022-30861-z
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    References listed on IDEAS

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    2. Yannick Simoni & Etienne Becht & Michael Fehlings & Chiew Yee Loh & Si-Lin Koo & Karen Wei Weng Teng & Joe Poh Sheng Yeong & Rahul Nahar & Tong Zhang & Hassen Kared & Kaibo Duan & Nicholas Ang & Micha, 2018. "Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates," Nature, Nature, vol. 557(7706), pages 575-579, May.
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