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Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma
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Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma
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Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma
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Journal Article
Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma
2024
Overview
Abstract
Context
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis in advanced stages. While therapies targeting the checkpoint molecules programmed cell death 1 (PD-1), its ligand PD-L1, and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have revolutionized treatment in many cancers, the results in ACCs were heterogeneous.
Objective
Their expression in ACC has not been systematically studied and might explain the variable response to immune checkpoint inhibitors.
Methods
The expression of PD-1, PD-L1 and CTLA-4 was examined in 162 tumor samples from 122 patients with ACC by immunohistochemistry (threshold of >1%) and correlated with tumoral T lymphocyte infiltration and clinical endpoints. Finally, univariate and multivariate analyses of progression-free and overall survival were performed.
Results
PD-1 and PD-L1 were expressed in 26.5% and 24.7% of samples, respectively, with low expression in most tumor samples (median positive cells: 2.1% and 21.7%). In contrast, CTLA-4 expression was observed in 52.5% of ACC with a median of 38.4% positive cells. Positive PD-1 expression was associated with longer progression-free survival (HR 0.50, 95% CI 0.25-0.98, P = .04) even after considering prognostic factors. In contrast, PD-L1 and CTLA-4 did not correlate with clinical outcome. Additionally, PD-1 and PD-L1 expression correlated significantly with the amount of CD3+, CD4+, FoxP3+, and CD8+ T cells.
Conclusion
The heterogeneous expression of PD1, PD-L1, and CTLA-4 in this large series of well-annotated ACC samples might explain the heterogeneous results of the immunotherapies in advanced ACC. In addition, PD-1 expression is a strong prognostic biomarker that can easily be applied in routine clinical care and histopathological assessment.
Publisher
Oxford University Press
Subject
/ Adrenal Cortex Neoplasms - immunology
/ Adrenal Cortex Neoplasms - metabolism
/ Adrenal Cortex Neoplasms - mortality
/ Adrenal Cortex Neoplasms - pathology
/ Adrenocortical Carcinoma - metabolism
/ Adrenocortical Carcinoma - mortality
/ Adrenocortical Carcinoma - pathology
/ Adult
/ Aged
/ Analysis
/ Biomarkers, Tumor - analysis
/ Biomarkers, Tumor - metabolism
/ Cancer
/ Clinical
/ Female
/ Humans
/ Immune checkpoint inhibitors
/ Lymphocytes, Tumor-Infiltrating - immunology
/ Lymphocytes, Tumor-Infiltrating - metabolism
/ Male
/ Programmed Cell Death 1 Receptor - metabolism
/ T cells
/ Tumors
