Clinical and prognostic implications of CD47 and PD-L1 expression in surgically resected small-cell lung cancer
C Lang1, A Lantos2, Z Megyesfalvi3
1Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Background:
Pharmacological inhibition of the immune-checkpoint molecule CD47 has shown promising results in preclinical small-cell lung cancer (SCLC) models, whereas anti-programmed death-ligand 1 (PD-L1) inhibitors have been recently implemented in the standard of care of advanced-stage SCLC patients. Nevertheless, the expression pattern, clinical relevance and prognostic implication of both CD47 and PD-L1 are rather controversial in surgically treated SCLC patients.
Materials And Methods:
In total, 104 Caucasian SCLC patients from two Central European thoracic centers were included in this study. CD47 and PD-L1 expression as well as the expression of the four major SCLC molecular subtype markers (ASCL1, NEUROD1, YAP1 and POU2F3) were measured by immunohistochemistry. Expression levels were independently evaluated and statistically correlated with clinicopathological data and survival.
Results:
Positive CD47 and PD-L1 expressions were seen in 84.6% and 9.6% of the samples, respectively. Meanwhile, the tumor-associated stroma was positive for PD-L1 in 59.6% of the cases. Stromal PD-L1 expression correlated with longer overall survival (OS) (versus PD-L1-negative stroma; median OS was 42 versus 14 months, respectively, P = 0.003) and was confirmed as an independent predictor of favorable outcome upon multivariate analysis (hazard ratio 0.530, 95% confidence interval 0.298-0.943, P = 0.031). Notably, neither CD47 nor PD-L1 presence was related to a distinct molecular SCLC subtype.
Conclusion:
CD47 shows a remarkably high expression while tumoral PD-L1 expression is generally low in surgically treated SCLC. Importantly, stromal PD-L1 expression may indicate a favorable clinical outcome and serve as a novel prognostic factor in these patients. Additional studies are warranted to further investigate the clinical impact of CD47 and PD-L1 expression in SCLC.
Insights
High CD47 expression is common in surgically treated small-cell lung cancer (SCLC), while tumoral PD-L1 is low. Stromal PD-L1 expression, however, predicts a favorable outcome and serves as a novel prognostic factor in SCLC patients.
Area of Science:
- Oncology
- Immunology
- Thoracic Surgery
Background:
- Immune-checkpoint molecule CD47 inhibition shows promise in preclinical small-cell lung cancer (SCLC) models.
- Anti-programmed death-ligand 1 (PD-L1) inhibitors are used for advanced-stage SCLC.
- CD47 and PD-L1 expression, clinical relevance, and prognostic implications are debated in surgically treated SCLC.
Purpose of the Study:
- To investigate the expression patterns of CD47 and PD-L1 in surgically treated SCLC.
- To determine the clinical relevance and prognostic implications of CD47 and PD-L1 expression.
- To correlate CD47 and PD-L1 expression with SCLC molecular subtypes.
Main Methods:
- 104 Caucasian SCLC patients from two European thoracic centers were analyzed.
- Immunohistochemistry was used to measure CD47, PD-L1, and SCLC molecular subtype markers (ASCL1, NEUROD1, YAP1, POU2F3).
- Expression levels were correlated with clinicopathological data and survival.
Main Results:
- CD47 was highly expressed (84.6%), while tumoral PD-L1 was low (9.6%).
- Stromal PD-L1 was positive in 59.6% of cases and correlated with longer overall survival (42 vs. 14 months).
- Stromal PD-L1 was an independent predictor of favorable outcome (HR 0.530, P=0.031); neither marker related to SCLC subtypes.
Conclusions:
- Surgically treated SCLC exhibits high CD47 and low tumoral PD-L1 expression.
- Stromal PD-L1 expression may indicate a favorable clinical outcome and serve as a novel prognostic factor.
- Further studies are needed to explore the clinical impact of CD47 and PD-L1 in SCLC.
