Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC
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Anti–programmed death 1 therapy
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 ¼ 13), six antibodypositive 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 CD8þ T-cell infiltration. In the validation cohort (n ¼ 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 ¼ 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 ¼ 0.4, p ¼ 0.01) and overall survival (hazard ratio ¼ 0.2, p ¼ 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.
This work was supported by grants from JSPS KAKENHI (15K09235, 16K18463, 16K21533, 18K15226, and 18K07306) to Drs. Oka, Ohue, and Kurose; by grants from the Takeda Science Foundation to Drs. Ohue and Kurose; by a grant from the Medical Research Encouragement Prize of The Japan Medical Association to Dr. Ohue; by a grant from the Okayama Health Foundation to Dr. Ohue; and by grants from Kawasaki Medical School to Drs. Oka, Ohue, and Kurose. Dr. Oka received collaborative research funds from the University of Tokyo and Thyas Co., Ltd. The Department of Immuno-Oncology is endowed by Pole Star Co., Ltd.
Journal of Thoracic Oncology
International Association for the Study of Lung Cancer
© 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).