Prognostic Value of Programmed Death Ligand-1 in Discriminating Patients With Lymph Node--Negative, p53--Wild-Type, or Low-BRCA1/2-Expression Pancreatic Ductal Adenocarcinoma.

Context.--Alterations in the tumor microenvironment affect the response to immunotherapy and are associated with clinical outcomes. However, the role of B7 family checkpoint molecules in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Objective.--To investigate the expression of programmed...

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Publicado en:Archives of Pathology & Laboratory Medicine Vol. 147; no. 4; pp. 465 - 474
Autores principales: Xianlong Chen, Yue Zhang, Shengwei Mo, Heng Ma, Zhaohui Lu, Shuangni Yu, Jie Chen
Formato: pictorial research tables/charts Journal Article
Publicado: College of American Pathologists Apr2023
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2023
      vid: 147
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      pub: College of American Pathologists
      place: Northfield, Illinois
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        10.5858/arpa.2021-0471-OA
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        atl: Prognostic Value of Programmed Death Ligand-1 in Discriminating Patients With Lymph Node--Negative, p53--Wild-Type, or Low-BRCA1/2-Expression Pancreatic Ductal Adenocarcinoma.
      aug:
        au:
          Xianlong Chen
          Yue Zhang
          Shengwei Mo
          Heng Ma
          Zhaohui Lu
          Shuangni Yu
          Jie Chen
        affil: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
      sug:
        subj:
          Adenocarcinoma Prognosis
          Carcinoma, Ductal Prognosis
          Pancreatic Neoplasms Prognosis
          Programmed Cell Death Ligand 1
          Gene Expression
          Genes, BRCA
          Human
          Descriptive Statistics
          Data Analysis Software
          Chi Square Test
          Fisher's Exact Test
          Kaplan-Meier Estimator
          Confidence Intervals
          Log-Rank Test
          Univariate Statistics
          Multivariate Analysis
          Cox Proportional Hazards Model
          Biological Assay
          Immunohistochemistry
      ab: Context.--Alterations in the tumor microenvironment affect the response to immunotherapy and are associated with clinical outcomes. However, the role of B7 family checkpoint molecules in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Objective.--To investigate the expression of programmed death ligand-1 (PD-L1), B7 homolog 3 (B7-H3), and B7 homolog 4 (B7-H4) and the association of these molecules with pathologic features, DNA damage repair (DDR) molecules, immune infiltrates, and survival in PDAC. Design.--The expression of B7 family molecules, densities of immune cells, and DDR status were evaluated by using immunohistochemical assays in tissue microarrays. Results.--Positive PD-L1 expression on tumor cells (TCs) and stromal cells (SCs) was observed in 30.3% (80 of 264) and 20.5% (54 of 264) of patients, respectively, whereas B7-H3 showed positivity in 81.3% (195 of 240) and 87.9% (211 of 240) of patients, respectively. B7-H4 was detected exclusively in tumor cells, with a positivity rate of 76.0% (193 of 254). PD-L1 on TCs was an independent predictor of worse disease-free survival, whereas B7-H3 on TCs was an independent factor of improved survival. The prognostic significance of PD-L1 was more discriminative in lymph node--negative, p53--wild-type, and low-BRCA1/2-expression tumors. B7-H3 on SCs was negatively correlated with CD45RO T cells, whereas PD-L1 on SCs was related to high densities of CD3, CD4, CD8, CD45RO, and Foxp3 T cells and B7-H4 was more common in tumors with a low CD8 status. Conclusions.--We identified B7 family checkpoint molecules as potentially prognostic indicators, combined with different DDR molecular statuses and complex immune infiltrates, in PDAC.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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