Identification of biomarkers for personalized peptide vaccination in 2,588 cancer patients

Suekane,Shigetaka; Yutani,Shigeru; Yamada,Akira; Sasada,Tetsuro; Matsueda,Satoko; Takamori,Shinzo; Toh,Uhi; Kawano,Kouichiro; Yoshiyama,Koichi; Sakamoto,Shinjiro; Sugawara,Shunichi; Komatsu,Nobukazu; Yamada,Teppei; Naito,Masayasu; Terasaki,Mizuhiko; Mine,Takashi; Itoh,Kyogo; Shichijo,Shigeki; Noguchi,Masanori

doi:10.3892/ijo.2020.5019

Identification of biomarkers for personalized peptide vaccination in 2,588 cancer patients

Authors:
- Shigetaka Suekane
- Shigeru Yutani
- Akira Yamada
- Tetsuro Sasada
- Satoko Matsueda
- Shinzo Takamori
- Uhi Toh
- Kouichiro Kawano
- Koichi Yoshiyama
- Shinjiro Sakamoto
- Shunichi Sugawara
- Nobukazu Komatsu
- Teppei Yamada
- Masayasu Naito
- Mizuhiko Terasaki
- Takashi Mine
- Kyogo Itoh
- Shigeki Shichijo
- Masanori Noguchi
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Affiliations: Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Cancer Vaccine Center, Kurume University, Kurume, Fukuoka 839‑0863, Japan, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka 830‑0011, Japan, Cancer Vaccine Center, Kanagawa Cancer Center, Yokohama, Kanagawa 241‑8515, Japan, Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY 14263, USA, Department of Surgery, Kurume University, Kurume, Fukuoka 830‑0011, Japan, Department of Obstetrics and Gynecology, Kurume University, Kurume, Fukuoka 830‑0011, Japan, Department of Molecular and Internal Medicine School of Medicine, Hiroshima University, Hiroshima, Hiroshima 734‑8551, Japan, Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Miyagi 980‑0873, Japan, Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Fukuoka, Fukuoka 814‑0180, Japan, Terasaki Neurosurgery Clinic, Chikugo, Fukuoka 833‑0031, Japan, Department of Clinical Oncology, Nagasaki Harbor Medical Center, Nagasaki, Nagasaki 850‑8555, Japan
Published online on: March 19, 2020 https://doi.org/10.3892/ijo.2020.5019
Pages: 1479-1489
Copyright: © Suekane et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Peptide‑based cancer vaccines have failed to provide sufficient clinical benefits in order to be approved in clinical trials since the 1990s. To understand the mechanisms underlying this failure, the present study investigated biomarkers associated with the lower overall survival (OS) among 2,588 patients receiving personalized peptide vaccination (PPV). Survival data were obtained from a database of 2,588 cancer patients including 399 patients with lung, 354 with prostate and 344 with colon cancer. They entered into phase II clinical trials of PPV in which 2 to 4 of 31 warehouse peptides were selected for vaccination on an individual patient basis based on human leukocyte antigen (HLA) class IA‑types and pre‑existing peptide‑specific IgG levels. Higher pre‑vaccination neutrophil, monocyte and platelet counts, and lower pre‑vaccination lymphocyte and red blood cell counts were inversely associated with OS, with higher sensitivities in the proportions of neutrophils and lymphocytes, respectively. The most potent unfavorable and favorable factors for OS were the median percentage of neutrophils (≥64.8%) or percentage of lymphocytes (≥25.1%) with correlation coefficients (R2) of 0.98 and 0.92, respectively. Higher pre‑vaccination levels of c‑reactive protein and other inflammatory soluble factors were inversely associated with OS. Pre‑vaccination peptide‑specific immunity levels had no effect on OS, although lower immune boosting levels were inversely associated with OS. None of the 31 peptides was inversely associated with OS, although a few peptides were positively associated with it. On the whole, the findings of the present study suggested that pre‑vaccination inflammatory signatures, but not those of post‑vaccination immune induction, were associated with lower clinical benefits of PPV.

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