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Ohue, Yoshihiro Department of Respiratory Medicine, Kawasaki Medical School
Kurose, Koji Department of Respiratory Medicine, Kawasaki Medical School
Karasaki, Takahiro Department of Thoracic Surgery, The University of Tokyo
Isobe, Midori Department of Respiratory Medicine, Kawasaki Medical School
Yamaoka, Takaaki Department of Respiratory Medicine, Kawasaki Medical School
Futami, Junichiro Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID Kaken ID publons researchmap
Irei, Isao Department of Pathology, Kawasaki Medical School
Masuda, Takeshi Department of Respiratory Internal Medicine, Hiroshima University Hospital
Fukuda, Masaaki Department of Respiratory Medicine, The Japanese Red Cross Nagasaki Genbaku Hospital
Kinoshita, Akitoshi Department of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital
Matsushita, Hirokazu Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo
Shimizu, Katsuhiko Department of General Thoracic Surgery, Kawasaki Medical School
Nakata, Masao Department of General Thoracic Surgery, Kawasaki Medical School
Hattori, Noboru Department of Respiratory Internal Medicine, Hiroshima University Hospital
Yamaguchi, Hiroyuki Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences
Fukuda, Minoru Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences
Nozawa, Ryohei Faculty of Health and Welfare Services Administration, Kawasaki University of Medical Welfare
Kakimi, Kazuhiro Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo
Oka, Mikio Department of Immuno-Oncology, Kawasaki Medical School
Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits.
Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing.
Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004).
Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers.
Anti-programmed death 1 therapy
Journal of Thoracic Oncology
© 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
|Web of Science KeyUT|
Ohue Y, Kurose K, Karasaki T, et al. Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti-Programmed Cell Death-1 Therapy in NSCLC. J Thorac Oncol. 2019;14(12):2071‐2083. doi:10.1016/j.jtho.2019.08.008