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Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC
Hidenobu Ishii1, Koichi Azuma1, Akihiko Kawahara2
1Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
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.
Insights
High CD73 expression predicts better outcomes for non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), particularly those with EGFR mutations. This finding offers new insights into predicting treatment response.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- CD73 facilitates immune evasion in malignancies by converting AMP to adenosine.
- CD73 overexpression is a known poor prognostic factor in various cancers, including non-small cell lung cancer (NSCLC).
- The predictive value of CD73 in NSCLC patients receiving immune checkpoint inhibitors (ICIs) remains unelucidated.
Purpose of the Study:
- To investigate the prognostic significance of CD73 expression in NSCLC patients undergoing treatment with ICIs.
- To determine if CD73 expression levels can predict treatment response and survival outcomes in this patient cohort.
Main Methods:
- Retrospective analysis of 91 patients with advanced or recurrent NSCLC treated with ICIs.
- Immunohistochemical evaluation of CD73 expression in pre-treatment tumor tissue specimens.
- Correlation of CD73 expression levels with progression-free survival (PFS) and overall survival (OS).
Main Results:
- Increased CD73 expression correlated with improved PFS and OS.
- Patients with high CD73 expression (≥50% tumor cells) demonstrated significantly better survival than those with lower expression (<50%).
- High CD73 expression predicted enhanced ICI efficacy in EGFR mutation-positive NSCLC, but not in EGFR mutation-negative NSCLC.
- CD73 expression was an independent predictor of PFS in EGFR mutation-positive patients, irrespective of PD-L1 status.
Conclusions:
- Elevated CD73 expression is associated with favorable responses to ICIs in NSCLC patients.
- CD73 expression serves as a potential predictive biomarker for ICI therapy, especially in NSCLC patients with EGFR mutations.
- These findings highlight the role of CD73 in modulating the tumor immune microenvironment and predicting immunotherapy outcomes.
