Evaluation of prognostic significance of granulocyte-related factors in cancer patients undergoing personalized peptide vaccination.
Since cancer vaccines do not always elicit beneficial effects in treated patients, identification of biomarkers for predicting clinical outcomes would be highly desirable. We previously reported that abnormal granulocytes present in peripheral blood mononuclear cells (PBMC) may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination (PPV). In the current study, we examined whether soluble factors derived from granulocytes, such as matrix metalloproteinase 9 (MMP-9), myeloperoxidase (MPO), and arginase 1 (ARG1), and inhibitory cytokine TGFβ in pre-vaccination plasma were useful for predicting prognosis after PPV in advanced cancer patients. In biliary tract cancer (n=25), multivariate Cox regression analysis demonstrated that patients with higher plasma MMP-9 levels had a significantly worse overall survival (OS) [hazard ratio (HR) = 4.637, 95% confidence interval (CI) = 1.670 - 12.877, P = 0.003], whereas MPO, ARG1, or TGFβ levels were not correlated with OS. Similarly, patients with higher MMP-9 levels showed worse prognosis than those with lower MMP-9 levels in other types of advanced cancers, including non-small cell lung cancer (n=32, P = 0.037 by log-rank test), and pancreatic cancer (n=41, P = 0.042 by log-rank test). Taken together, plasma MMP-9 levels before vaccination might be potentially useful as a biomarker for selecting advanced cancer patients who would benefit from PPV.
a Research Center for Innovative Cancer Therapy; Kurume University ; Kurume , Japan.|b Cancer Vaccine Center; Kurume University ; Kurume , Japan.|c Department of Molecular and Internal Medicine ; Institute of Biomedical & Health Sciences; Hiroshima University ; Hiroshima , Japan.
Shinjiro
S
Sakamoto
d Department of Surgery ; Kurume University School of Medicine ; Kurume , Japan.
Munehiro
M
Yoshitomi
b Cancer Vaccine Center; Kurume University ; Kurume , Japan.
Shigeru
S
Yutani
d Department of Surgery ; Kurume University School of Medicine ; Kurume , Japan.
Yasuhiro
Y
Terazaki
d Department of Surgery ; Kurume University School of Medicine ; Kurume , Japan.
Koichi
K
Yoshiyama
b Cancer Vaccine Center; Kurume University ; Kurume , Japan.
Tetsuya
T
Ioji
b Cancer Vaccine Center; Kurume University ; Kurume , Japan.
Satoko
S
Matsueda
a Research Center for Innovative Cancer Therapy; Kurume University ; Kurume , Japan.
Akira
A
Yamada
d Department of Surgery ; Kurume University School of Medicine ; Kurume , Japan.
Shinzo
S
Takamori
b Cancer Vaccine Center; Kurume University ; Kurume , Japan.
Kyogo
K
Itoh
c Department of Molecular and Internal Medicine ; Institute of Biomedical & Health Sciences; Hiroshima University ; Hiroshima , Japan.
Noboru
N
Hattori
c Department of Molecular and Internal Medicine ; Institute of Biomedical & Health Sciences; Hiroshima University ; Hiroshima , Japan.
Nobuoki
N
Kohno
b Cancer Vaccine Center; Kurume University ; Kurume , Japan.|e Kanagawa Cancer Center Research Institute ; Yokohama , Japan.
Tetsuro
T
Sasada
D001119:Arginase / Q000097:blood; D001661:Biliary Tract Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009195:Peroxidase / Q000097:blood; D057285:Precision Medicine / Q000379:methods; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000097:blood; D022223:Vaccines, Subunit / Q000627:therapeutic use*
D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D016212:Transforming Growth Factor beta; D022223:Vaccines, Subunit; D009195:Peroxidase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D001119:Arginase
ARG1; MMP-9; MPO; biomarker; multivariate Cox regression analysis; personalized peptide vaccine