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Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC

BACKGROUND: CD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non‐small cell lung cancer (...

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Autores principales: Ishii, Hidenobu, Azuma, Koichi, Kawahara, Akihiko, Kinoshita, Takashi, Matsuo, Norikazu, Naito, Yoshiko, Tokito, Takaaki, Yamada, Kazuhiko, Akiba, Jun, Hoshino, Tomoaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113063/
https://www.ncbi.nlm.nih.gov/pubmed/32061060
http://dx.doi.org/10.1111/1759-7714.13346
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author Ishii, Hidenobu
Azuma, Koichi
Kawahara, Akihiko
Kinoshita, Takashi
Matsuo, Norikazu
Naito, Yoshiko
Tokito, Takaaki
Yamada, Kazuhiko
Akiba, Jun
Hoshino, Tomoaki
author_facet Ishii, Hidenobu
Azuma, Koichi
Kawahara, Akihiko
Kinoshita, Takashi
Matsuo, Norikazu
Naito, Yoshiko
Tokito, Takaaki
Yamada, Kazuhiko
Akiba, Jun
Hoshino, Tomoaki
author_sort Ishii, Hidenobu
collection PubMed
description BACKGROUND: CD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non‐small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs). METHODS: We screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs. RESULTS: Analysis of progression‐free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD‐L1 expression in patients with EGFR mutation. CONCLUSIONS: High CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations. KEY POINTS: Significant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. What this study adds: High CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations.
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spelling pubmed-71130632020-04-02 Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC Ishii, Hidenobu Azuma, Koichi Kawahara, Akihiko Kinoshita, Takashi Matsuo, Norikazu Naito, Yoshiko Tokito, Takaaki Yamada, Kazuhiko Akiba, Jun Hoshino, Tomoaki Thorac Cancer Original Articles BACKGROUND: CD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non‐small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs). METHODS: We screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs. RESULTS: Analysis of progression‐free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD‐L1 expression in patients with EGFR mutation. CONCLUSIONS: High CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations. KEY POINTS: Significant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. What this study adds: High CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations. John Wiley & Sons Australia, Ltd 2020-02-15 2020-04 /pmc/articles/PMC7113063/ /pubmed/32061060 http://dx.doi.org/10.1111/1759-7714.13346 Text en © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Ishii, Hidenobu
Azuma, Koichi
Kawahara, Akihiko
Kinoshita, Takashi
Matsuo, Norikazu
Naito, Yoshiko
Tokito, Takaaki
Yamada, Kazuhiko
Akiba, Jun
Hoshino, Tomoaki
Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
title Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
title_full Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
title_fullStr Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
title_full_unstemmed Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
title_short Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
title_sort predictive value of cd73 expression for the efficacy of immune checkpoint inhibitors in nsclc
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113063/
https://www.ncbi.nlm.nih.gov/pubmed/32061060
http://dx.doi.org/10.1111/1759-7714.13346
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