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Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

 Sung Gwe Ahn  ;  Seon-Kyu Kim  ;  Jonathan H Shepherd  ;  Yoon Jin Cha  ;  Soong June Bae  ;  Chungyeul Kim  ;  Joon Jeong  ;  Charles M Perou 
 BREAST CANCER RESEARCH AND TREATMENT, Vol.188(1) : 165-178, 2021-07 
Journal Title
Issue Date
B7-H1 Antigen* ; Genomics ; Humans ; Immunohistochemistry ; Prognosis ; Triple Negative Breast Neoplasms*
Immune-check point inhibitors ; SP142 PD-L1 ; Triple-negative breast cancer ; Tumor-infiltrating lymphocytes
Purpose: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients.

Methods: Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI).

Results: Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival.

Conclusions: We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Bae, Soong June(배숭준) ORCID logo https://orcid.org/0000-0002-0012-9694
Ahn, Sung Gwe(안성귀) ORCID logo https://orcid.org/0000-0002-8778-9686
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
Cha, Yoon Jin(차윤진) ORCID logo https://orcid.org/0000-0002-5967-4064
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