ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2022
Heterogeneity of programmed death-ligand 1 expression and infiltrating lymphocytes in paired resected primary and metastatic non-small cell lung cancer.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- Image-based PD-L1 scoring and tumor-infiltrating lymphocytes as predictors for the response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Soluble PD-L1 (sPD-L1) as a biomarker of durable response and survival in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitors (ICIs).Cancer immunology, immunotherapy : CII · 2025Article
- 68Ga-NK224 PET/CT for Noninvasive Evaluation of PD-L1 Expression and Intertumor Heterogeneity: A Translational Exploratory Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Spatial Heterogeneity of PD-L1 Expression as a Biomarker for Third-Generation EGFR-TKI Response in Advanced EGFR-Mutant NSCLC.Cancer science · 2025Article
- The predictive value of total body PET/CT in high PD-L1 expression and immunotherapy in advanced non-small cell lung cancer patients.Frontiers in oncology · 2025Article
- Discrepancies in PD-L1 expression, lymphocyte infiltration, and tumor mutational burden in non-small cell lung cancer and matched brain metastases.Translational lung cancer research · 2024Article
- The roles of PD-L1 in the various stages of tumor metastasis.Cancer metastasis reviews · 2024Review
- Impact of platinum-based chemotherapy on the tumor mutational burden and immune microenvironment in non-small cell lung cancer with postoperative recurrence.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases.British journal of cancer · 2024Review
- Spatial and temporal heterogeneity of tumor immune microenvironment between primary tumor and brain metastases in NSCLC.BMC cancer · 2024Article
- [Comparative Study of PD-L1 Expression in Different Sites of Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Article
- Choosing the optimal immunotherapeutic strategies for non-small cell lung cancer based on clinical factors.Frontiers in oncology · 2022Review
- PD-L1 expression on circulating tumor cells can be a predictive biomarker to PD-1 inhibitors combined with radiotherapy and antiangiogenic therapy in advanced hepatocellular carcinoma.Frontiers in oncology · 2022Article
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastatic tumors (MTs) may show different characteristics of the immune microenvironment from primary tumors (PTs) in non-small cell lung cancer (NSCLC). The heterogeneity of immune markers in metastatic NSCLC and its associated factors has not been well demonstrated. In this study, 64 surgically resected specimens of paired PTs and MTs were obtained from 28 patients with NSCLC. Multiplex immunofluorescence (mIF; panel including programmed death-ligand 1 (PD-L1), Cytokeratin, CD8, and CD68) was performed on whole sections. The heterogeneity of the immune contexture of PD-L1 expression, infiltrating lymphocytes, and immune-to-tumor cell distances was quantified via digital image analysis. In a quantitative comparison of MTs and corresponding PTs, MTs showed higher PD-L1 expression levels, lower density of CD8+ cytotoxic T lymphocytes (CTLs), and longer spatial distance between CTLs and tumor cells. Subgroup analysis, which associated clinical factors, revealed that the heterogeneity of immune markers was more obvious in extrapulmonary, metachronous, and treated MTs, while fewer differences were observed in intrapulmonary, synchronous, and untreated MTs. In particular, MTs showed significantly higher PD-L1 expression and lower lymphocyte infiltration in metastatic NSCLC with EGFR mutations. Prognosis analysis showed that an increased density of CD8+ CTLs in MTs was associated with better overall survival (OS). Therefore, significant discrepancies in PD-L1 expression and lymphocyte infiltration in metastatic NSCLC are most likely associated with temporal heterogeneity with a history of anti-treatment and correlated with EGFR mutations. The detection of immune markers in re-obtained metastatic specimens may be required for immunotherapy prediction in these patients with metastatic NSCLC.
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