Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC

Yoshihiro Ohue, Koji Kurose, Takahiro Karasaki, Midori Isobe, Takaaki Yamaoka, Junichiro Futami, Isao Irei, Takeshi Masuda, Masaaki Fukuda, Akitoshi Kinoshita, Hirokazu Matsushita, Katsuhiko Shimizu, Masao Nakata, Noboru Hattori, Hiroyuki Yamaguchi, Minoru Fukuda, Ryohei Nozawa, Kazuhiro Kakimi, Mikio Oka

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Thoracic Oncology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Cell Death
Antigens
Antibodies
Serum
Survival
Biomarkers
Therapeutics
Disease-Free Survival
Ligands
Neoplasms
Mutation
Tumor Microenvironment
Testicular Neoplasms
Tumor Biomarkers
Multivariate Analysis
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Prospective Studies
T-Lymphocytes

Keywords

  • Anti–programmed death 1 therapy
  • Biomarker
  • Cancer-testis antigen
  • NSCLC
  • Serum antibody

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC. / Ohue, Yoshihiro; Kurose, Koji; Karasaki, Takahiro; Isobe, Midori; Yamaoka, Takaaki; Futami, Junichiro; Irei, Isao; Masuda, Takeshi; Fukuda, Masaaki; Kinoshita, Akitoshi; Matsushita, Hirokazu; Shimizu, Katsuhiko; Nakata, Masao; Hattori, Noboru; Yamaguchi, Hiroyuki; Fukuda, Minoru; Nozawa, Ryohei; Kakimi, Kazuhiro; Oka, Mikio.

In: Journal of Thoracic Oncology, 01.01.2019.

Research output: Contribution to journalArticle

Ohue, Y, Kurose, K, Karasaki, T, Isobe, M, Yamaoka, T, Futami, J, Irei, I, Masuda, T, Fukuda, M, Kinoshita, A, Matsushita, H, Shimizu, K, Nakata, M, Hattori, N, Yamaguchi, H, Fukuda, M, Nozawa, R, Kakimi, K & Oka, M 2019, 'Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC', Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2019.08.008
Ohue, Yoshihiro ; Kurose, Koji ; Karasaki, Takahiro ; Isobe, Midori ; Yamaoka, Takaaki ; Futami, Junichiro ; Irei, Isao ; Masuda, Takeshi ; Fukuda, Masaaki ; Kinoshita, Akitoshi ; Matsushita, Hirokazu ; Shimizu, Katsuhiko ; Nakata, Masao ; Hattori, Noboru ; Yamaguchi, Hiroyuki ; Fukuda, Minoru ; Nozawa, Ryohei ; Kakimi, Kazuhiro ; Oka, Mikio. / Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC. In: Journal of Thoracic Oncology. 2019.
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abstract = "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.",
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T1 - Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC

AU - Ohue, Yoshihiro

AU - Kurose, Koji

AU - Karasaki, Takahiro

AU - Isobe, Midori

AU - Yamaoka, Takaaki

AU - Futami, Junichiro

AU - Irei, Isao

AU - Masuda, Takeshi

AU - Fukuda, Masaaki

AU - Kinoshita, Akitoshi

AU - Matsushita, Hirokazu

AU - Shimizu, Katsuhiko

AU - Nakata, Masao

AU - Hattori, Noboru

AU - Yamaguchi, Hiroyuki

AU - Fukuda, Minoru

AU - Nozawa, Ryohei

AU - Kakimi, Kazuhiro

AU - Oka, Mikio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Anti–programmed death 1 therapy

KW - Biomarker

KW - Cancer-testis antigen

KW - NSCLC

KW - Serum antibody

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