ArticleDiagnostic pathology2018
Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors.
Article in Diagnostic pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.Cells · 2020Pooled it
- Prognostic value of the common tumour-infiltrating lymphocyte subtypes for patients with non-small cell lung cancer: A meta-analysis.PloS one · 2020Pooled it
- Poor Lymphocyte Infiltration to Primary Tumors in Acral Lentiginous Melanoma and Mucosal Melanoma Compared to Cutaneous Melanoma.Frontiers in oncology · 2020Pooled it
- Digital Immunophenotyping of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Subtypes With Specific Tumor-Immune Microenvironment Features.Endocrine pathology · 2025Article
- HLA-I genotype landscape in lung cancer and its prognosis value in Chinese small cell lung cancer.Scientific reports · 2025Article
- The current and emerging immunotherapy paradigm in small-cell lung cancer.Nature cancer · 2025Review
- A four gene risk score model for prognosis and immune microenvironment insights in small cell lung cancer based on CAF functional-related genes.Discover oncology · 2025Article
- Whole-section digital analysis of immune profiles in surgically resected small cell lung carcinoma and their associations with molecular subtypes.Translational lung cancer research · 2025Article
- Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.Frontiers in oncology · 2024Article
- C-Myc-induced hypersialylation of small cell lung cancer facilitates pro-tumoral phenotypes of macrophages.iScience · 2023Article
- Narrative Review of Immunotherapy in Gastroentero-Pancreatic Neuroendocrine Neoplasms.Current oncology (Toronto, Ont.) · 2023Review
- Progress in radiotherapy for small-cell lung cancer.Precision radiation oncology · 2023Review
- T lymphocyte cell: A pivotal player in lung cancer.Frontiers in immunology · 2023Review
- Infiltrating T lymphocytes in the tumor microenvironment of small cell lung cancer: a state of knowledge review.Journal of cancer research and clinical oncology · 2022Review
- Immune Checkpoint Blockade in Lung Carcinoids with Aggressive Behaviour: One More Arrow in Our Quiver?Journal of clinical medicine · 2022Review
- Current status and future perspectives of immune checkpoint inhibitors in extensive-stage small cell lung cancer.American journal of cancer research · 2022Review
- Clinical implications of immune checkpoint markers and immune infiltrates in patients with thymic neuroendocrine neoplasms.Frontiers in oncology · 2022Article
- The efficacy of immune checkpoint inhibitors in thoracic malignancies.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Small-Cell Lung Cancer Long-Term Survivor Patients: How to Find a Needle in a Haystack?International journal of molecular sciences · 2021Review
- Prognostic value of programmed cell death ligand-1 expression in the tumor-infiltrating immune cells of patients with lung cancer: A meta-analysis.Molecular and clinical oncology · 2021Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors.
methodsIn total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 in these cases. Cases demonstrating ≥5% tumor cell expression or any expression (> 1%) of PD-L1 on immune cells were considered positive. CD8+ TILs both within stroma and tumor areas of invasive carcinoma were analyzed using whole-slide digital imaging. Manual regional annotation and machine cell counts were performed for each case.
resultsPositive expression of PD-L1 was observed in 72 cases (45.3%), including 9 cases (5.7%) with expression exclusively on tumor cells, 46 cases (28.9%) with expression exclusively on immune cells, and 17 cases (10.7%) with the expression on tumor cells and immune cells. PD-L1 expression was associated with necrosis (p < 0.001), high pathologic grade (p < 0.001) and histologic type (p < 0.001). No correlation was observed with overall survival (OS) (p = 0.158) or progression-free survival (PFS) (p = 0.315). In contrast, higher CD8+ T cell density was associated with the absence of vascular invasion (p = 0.004), histologic type (p = 0.005), negative lymph node metastasis (p = 0.005) and lower clinical staging (p = 0.007). Moreover, multivariate analysis revealed that CD8+ stromal TIL was an independent prognostic factor for improved OS (p = 0.009) and PFS (p = 0.002).
conclusionPD-L1 was expressed in approximately half of the PNETs. The majority of the expression was observed in immune cells. Positive expression of PD-L1 showed no correlation with OS or PFS, while higher CD8+ TILs within stroma was proved to be an independent prognostic factor for favorable OS and PFS of PNETs.
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