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Peptide vaccinations elicited strong immune responses that were reboosted by anti-PD1 therapy in a patient with myxofibrosarcoma

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Abstract

Peptide-based immunotherapy does not usually elicit strong immunological and clinical responses in patients with end-stage cancer, including sarcoma. Here we report a myxofibrosarcoma patient who showed a strong clinical response to peptide vaccinations and whose immune responses were reboosted by anti-PD1 therapy combined with peptide vaccinations. The 46-year-old man showed a strong response to the peptide vaccinations (papillomavirus binding factor peptide, survivin-2B peptide, incomplete Freund’s adjuvant, and polyethylene glycol-conjugated interferon-alpha 2a) and subsequent wide necrosis and massive infiltration of CD8+ T cells in a recurrent tumor. The patient’s immune responses weakened after surgical resection; however, they were reboosted following the administration of nivolumab combined with peptide vaccinations. Thus, anti-PD1 therapy combined with peptide vaccinations might be beneficial, as suggested by the observations in this sarcoma patient.

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Abbreviations

CT:

Computed tomography

HIV:

Human immunodeficiency virus

IFA:

Incomplete Freund’s adjuvant

MFH:

Malignant fibrous histiocytoma

MFS:

Myxofibrosarcoma

PBF:

Papillomavirus binding factor

PD1:

Programmed cell death 1

PDL1:

Programmed cell death ligand 1

PEG:

Polyethylene glycol

PET-CT:

Positron emission tomography-computed tomography

SVN-2B:

Survivin-2B

TAM:

Tumor-associated macrophage

TIL:

Tumor-infiltrating lymphocyte

TRBV:

T cell receptor beta variable

UPS:

Undifferentiated pleomorphic sarcoma

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Acknowledgements

The authors thank the staff of the Japanese Red Cross Hokkaido Block Blood Center for their kind donation of human sera.

Funding

This work was supported by grants from the Japan Society for the Promotion of Science Grants-in-aid for Scientific Research (KAKENHI) 16H05451 (to T. Tsukahara) and 17H01540 (to T. Torigoe), the Takeda Science Foundation (2018-Kenkyu-Shorei to T. Tsukahara), and a grant-in-aid from the Ono Cancer Research Fund (2017-3 to T. Tsukahara).

Author information

Author notes

  1. Hidekazu Kameshima

    Present address: Odori Breast Thyroid Gland Clinic, 11, South-1, West-6, Chuo-ku, Sapporo, 060-0061, Japan

  2. Ryo Hatae

    Present address: Department of Surgery, Fuchinobe General Hospital, 3-2-8, Fuchinobe, Sagamihara, 252-0206, Japan

  3. Munehide Nakatsugawa

    Present address: Department of Diagnostic Pathology, Tokyo Medical University Hachioji Medical Center, 1163 Tate-machi, Hachioji, 193-0998, Japan

Authors and Affiliations

  1. Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan

    Tomohide Tsukahara, Kazue Watanabe, Kenji Murata, Akari Takahashi, Emi Mizushima, Yuji Shibayama, Aiko Murai, Munehide Nakatsugawa, Terufumi Kubo, Takayuki Kanaseki, Yoshihiko Hirohashi, Noriyuki Sato & Toshihiko Torigoe

  2. Department of Cancer Immunology, Medical and Biological, Laboratories Co., Ltd, 1063-103 Terasawaoka, Ina, 396-0002, Japan

    Kazue Watanabe

  3. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan

    Kenji Murata, Emi Mizushima & Yuji Shibayama

  4. Surgery Branch, Higashi-Sapporo Hospital, 7-35, 3-3 Higashi-Sapporo, Shiroishi-ku, Sapporo, 003-8585, Japan

    Hidekazu Kameshima

  5. Department of Surgery, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, 189-0021, Japan

    Ryo Hatae & Yasuo Ohno

  6. Department of Pathology, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, 189-0021, Japan

    Rituko Kawahara

  7. Oncology Branch, Higashi-Sapporo Hospital, 7-35, 3-3 Higashi-Sapporo, Shiroishi-ku, Sapporo, 003-8585, Japan

    Takeshi Terui

  8. Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan

    Hiroko Asanuma & Tadashi Hasegawa

Authors
  1. Tomohide Tsukahara
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  2. Kazue Watanabe
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Contributions

TT designed the study, TT, KW, KM, AT, HA, and TH acquired the data, EM, YS, and AM prepared the samples, HK, RH, YO, and TT managed the patients, RK provided the materials, MN, TK, TK, and YH interpreted the data, TT wrote the manuscript, and NS and TT supervised the study.

Corresponding author

Correspondence to Tomohide Tsukahara.

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Conflict of interest

Tomohide Tsukahara, Yoshihiko Hirohashi, Takayuki Kanaseki, Munehide Nakatsugawa, Terufumi Kubo, and Toshihiko Torigoe received financial support through collaboration with Ono Pharmaceutical Co., Ltd. Tomohide Tsukahara, Yoshihiko Hirohashi, Takayuki Kanaseki, and Toshihiko Torigoe received financial support through collaboration with Medical Biological Laboratories Co., Ltd. The authors declare that there are no other conflicts of interest.

Ethical approval and ethical standards

This study was performed in accordance with the guidelines established by the Declaration of Helsinki and approved by the Ethics Committees of Higashi-Sapporo Hospital (260630) and Sapporo Medical University (282-156).

Informed consent

The patient and his family provided written informed consent for the use of tumor and blood samples in our research and for publication. Blood from healthy donors was collected by the Japanese Red Cross Hokkaido Block Blood Center after obtaining informed consent from the donors for research purposes.

Cell line authentication

C1R-A24 cells (C1R cells transfected with HLA-A*24:02 cDNA) were kindly provided by Dr. M. Takiguchi (Kumamoto University School of Medicine, Japan). C1R-A24 cells were authenticated by HLA typing.

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Tsukahara, T., Watanabe, K., Murata, K. et al. Peptide vaccinations elicited strong immune responses that were reboosted by anti-PD1 therapy in a patient with myxofibrosarcoma. Cancer Immunol Immunother 69, 189–197 (2020). https://doi.org/10.1007/s00262-019-02455-0

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  • DOI: https://doi.org/10.1007/s00262-019-02455-0

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