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Published on: September 25, 2018
CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma
Pedro Rocha1,2, Ruth Salazar1, Jiexin Zhang3
1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Boulevard, Houston, TX, 77030, USA.
Introduction:
CD73 is a membrane-bound enzyme crucial in adenosine generation. The adenosinergic pathway plays a critical role in immunosuppression and in anti-tumor effects of immune checkpoint inhibitors (ICI). Here, we interrogated CD73 expression in a richly annotated cohort of human lung adenocarcinoma (LUAD) and its association with clinicopathological, immune, and molecular features to better understand the role of this immune marker in LUAD pathobiology.
Materials And Methods:
Protein expression of CD73 was evaluated by immunohistochemistry in 106 archived LUADs from patients that underwent surgical treatment without neoadjuvant therapy. Total CD73 (T +) was calculated as the average of luminal (L +) and basolateral (BL +) percentage membrane expression scores for each LUAD and was used to classify tumors into three groups based on the extent of T CD73 expression (high, low, and negative).
Results:
CD73 expression was significantly and progressively increased across normal-appearing lung tissue, adenomatous atypical hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and LUAD. In LUAD, BL CD73 expression was associated with an increase in PD-L1 expression in tumor cells and increase of tumor-associated immune cells. Stratification of LUADs based on T CD73 extent also revealed that tumors with high expression of this enzyme overall exhibited significantly elevated immune infiltration and PD-L1 protein expression. Immune profiling demonstrated that T-cell inflammation and adenosine signatures were significantly higher in CD73-expressing lung adenocarcinomas relative to those lacking CD73.
Conclusion:
Our study suggests that higher CD73 expression is associated with an overall augmented host immune response, suggesting potential implications in the immune pathobiology of early stage lung adenocarcinoma. Our findings warrant further studies to explore the role of CD73 in immunotherapeutic response of LUAD.
Insights
Higher CD73 expression in lung adenocarcinoma correlates with increased immune cell infiltration and PD-L1, suggesting a role in the host immune response. Further research is needed to explore its impact on immunotherapy for lung adenocarcinoma.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- CD73 is a membrane-bound enzyme vital for adenosine generation.
- The adenosinergic pathway influences immunosuppression and anti-tumor immunity, particularly with immune checkpoint inhibitors (ICI).
Purpose of the Study:
- To investigate CD73 expression in lung adenocarcinoma (LUAD).
- To associate CD73 with clinicopathological, immune, and molecular features in LUAD.
- To understand the role of CD73 in LUAD pathobiology.
Main Methods:
- Immunohistochemistry was used to evaluate CD73 protein expression in 106 LUAD samples.
- Total CD73 expression was calculated and tumors were stratified into high, low, and negative groups.
- Associations with clinicopathological, immune, and molecular features were analyzed.
Main Results:
- CD73 expression increased progressively from normal lung tissue to LUAD.
- Basolateral CD73 expression correlated with increased PD-L1 and tumor-associated immune cells.
- High CD73 expression was linked to elevated immune infiltration, PD-L1 levels, T-cell inflammation, and adenosine signatures.
Conclusions:
- Increased CD73 expression is associated with a heightened host immune response in early-stage LUAD.
- These findings suggest potential implications for CD73 in LUAD immune pathobiology.
- Further studies are warranted to explore CD73's role in LUAD immunotherapeutic response.
