ArticleBiology2021
Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer.
Article in Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- The Promoting Angiogenesis and Its Clinical Significance of CD33Chronic diseases and translational medicine · 2026Article
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- From description to prediction: a multi-database bibliometric forecast-validation study of lung cancer and tumor-associated macrophages research (2005-2025).Frontiers in immunology · 2026Review
- Small cell lung cancer: from immunobiological mechanisms to clinical advances.Frontiers in immunology · 2026Review
- MET pathway inhibition increases chemo-immunotherapy efficacy in small cell lung cancer.Cell reports. Medicine · 2025Article
- Molecular heterogeneity of small cell lung cancer and new therapeutic possibilities: a narrative review of the literature.Translational lung cancer research · 2025Review
- Article
- Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin-etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment.Journal for immunotherapy of cancer · 2024Article
- Identification of RNA-binding protein YBX3 as an oncogene in clear cell renal cell carcinoma.Functional & integrative genomics · 2023Article
- Slit2/Robo1 signaling inhibits small-cell lung cancer by targeting β-catenin signaling in tumor cells and macrophages.Molecular oncology · 2023Article
- Increased TIM-3 expression in tumor-associated macrophages predicts a poorer prognosis in non-small cell lung cancer: a retrospective cohort study.Journal of thoracic disease · 2023Article
- Protein Expression of immune checkpoints STING and MHCII in small cell lung cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Article
- RISING STARS: Heterogeneity and the tumor microenvironment in neuroendocrine prostate cancer.The Journal of endocrinology · 2023Review
- BRAF RNA is prognostic and widely expressed in lung adenocarcinoma.Translational lung cancer research · 2023Article
- The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes.Cancer cell international · 2022Article
- EZCancerTarget: an open-access drug repurposing and data-collection tool to enhance target validation and optimize international research efforts against highly progressive cancers.BioData mining · 2022Article
- Technique integration of single-cell RNA sequencing with spatially resolved transcriptomics in the tumor microenvironment.Cancer cell international · 2022Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
This study aims to characterize tumor-infiltrating macrophages (TAMs), myeloid-derived suppressor cells (MDSC), and the related molecular milieu regulating anti-tumor immunity in limited-stage neuroendocrine (NE)-high and NE-low small cell lung cancer. Primary tumors and matched lymph node (LN) metastases of 32 resected, early-stage SCLC patients were analyzed by immunohistochemistry (IHC) with antibodies against pan-macrophage marker CD68, M2-macrophage marker CD163, and MDSC marker CD33. Area-adjusted cell counting on TMAs showed that TAMs are the most abundant cell type in the TME, and their number in tumor nests exceeds the number of CD3 + T-cells (64% vs. 38% in NE-low and 71% vs. 18% in NE-high). Furthermore, the ratio of CD163-expressing M2-polarized TAMs in tumor nests was significantly higher in NE-low vs. NE-high tumors (70% vs. 31%). TAM density shows a strong positive correlation with CD45 and CD3 in tumor nests, but not in the stroma. fGSEA analysis on a targeted RNAseq oncological panel of 2560 genes showed that NE-high tumors exhibited increased enrichment in pathways related to cell proliferation, whereas in NE-low tumors, immune response pathways were significantly upregulated. Interestingly, we identified a subset of NE-high tumors representing an immune-oasis phenotype, but with a different gene expression profile compared to NE-low tumors. In contrast, we found that a limited subgroup of NE-low tumors is immune-deserted and express distinct cellular pathways from NE-high tumors. Furthermore, we identified potential molecular targets based on our expression data in NE-low and immune-oasis tumor subsets, including CD70, ANXA1, ITGB6, TP63, IFI27, YBX3 and CXCR2.
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