PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer.
Clin Cancer Res
; 26(20): 5456-5461, 2020 10 15.
Article
em En
| MEDLINE
| ID: mdl-32709714
ABSTRACT
PURPOSE:
In both the IMpassion 130 trial in the metastatic setting and in Keynote 522 in the neoadjuvant setting, patients with triple-negative breast cancer (TNBC) showed benefit from PD-1 axis immunotherapy. Here, we assess PD-L1 expression on both tumor and immune cells using quantitative immunofluorescence to assess association with benefit from neoadjuvant durvalumab concurrent with chemotherapy in TNBC. EXPERIMENTALDESIGN:
Pretreatment core needle biopsies (n = 69) were obtained from patients who participated in a phase I/II clinical trial (NCT02489448). The final analysis included 45 patients [pathologic complete response (pCR) = 18, non-pCR = 27] due to technical issues and insufficient tissue. Slides were stained using a previously validated Ultivue DNA-based Ultimapper kit (CD8, CD68, PD-L1, Cytokeratin/Sox10, and Hoechst counterstain). The PD-L1 expression was analyzed by molecular compartmentalization without segmentation using AQUA software (version 3.2.2.1) in three tissue compartments including tumor (cytokeratin-positive cells), CD68+ cells, and overall stroma.RESULTS:
In patients with pCR, PD-L1 expression was significantly higher in tumor cells, in CD68+ cells and in the stroma compared with patients non-pCR. There was no difference in the amount of CD68+ cells in the tumor or stromal compartments between cases with pCR and non-pCR.CONCLUSIONS:
Expression of PD-L1 in tumor cells, immune cells in stroma, and colocalized with CD68+ cells is associated with higher rates of pCR to durvalumab and chemotherapy in TNBC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Diferenciação Mielomonocítica
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Antígenos CD
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Antígeno B7-H1
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Receptor de Morte Celular Programada 1
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Neoplasias de Mama Triplo Negativas
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Anticorpos Monoclonais
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article