ArticleCancer research2023
Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 41 citations in OpenAlex.
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- AI-powered and manual assessment of tumor-infiltrating lymphocytes in early HER2-positive breast cancer in NSABP B-41.NPJ breast cancer · 2026Article
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- Single-cell spatial transcriptomics reveals tumor microenvironment heterogeneity in primary and lymph node-metastatic small cell lung cancer.Cell reports. Medicine · 2026Article
- Research progress of tertiary lymphoid structure in hepatocellular carcinoma: from prognostic biomarkers to new strategies for immunotherapy.Frontiers in immunology · 2026Review
- Functional, Pharmacogenomic, and Immune Landscapes of Long Non-Coding RNAs in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Metabolic heterogeneity in tumor cells impacts immunology in lung squamous cell carcinoma.Oncoimmunology · 2025Article
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Short-term intra- and peri-tumoral spatiotemporal CT radiomics for predicting major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.European radiology · 2025Article
- Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy.Translational lung cancer research · 2025Review
- Mendelian randomization analyses support causal relationships between unswitched memory B cells and lung squamous cell carcinoma.Discover oncology · 2025Article
- A fibroblast-centric network drives cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Distilling knowledge from graph neural networks trained on cell graphs to non-neural student models.Scientific reports · 2025Article
- Tumor antigens preferentially derive from unmutated genomic sequences in melanoma and non-small cell lung cancer.Nature cancer · 2025Article
- Induced B cell receptor diversity predicts PD-1 blockade immunotherapy response.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tumor-infiltrating B cells in non-small cell lung cancer: current insights and future directions.Cancer cell international · 2025Review
- Spatially mapping the tumour immune microenvironments of non-small cell lung cancer.Nature communications · 2025Article
- Tertiary lymphoid structures in renal cell carcinoma: from heterogeneity dissection to translational precision immunotherapy.Frontiers in immunology · 2025Review
- Analysis of single-cell and spatial transcriptomics in TNBC cell-cell interactions.Frontiers in immunology · 2025Review
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Beyond tertiary lymphoid structures, a significant number of immune-rich areas without germinal center-like structures are observed in non-small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, and constitution of immune rich areas (immune hotspots) in a cohort of 935 patients with lung cancer from The Cancer Genome Atlas. A high intratumoral immune hotspot score, which measures the proportion of immune hotspots interfacing with tumor islands, was correlated with poor overall survival in lung squamous cell carcinoma but not in lung adenocarcinoma. Lung squamous cell carcinomas with high intratumoral immune hotspot scores were characterized by consistent upregulation of B-cell signatures. Spatial statistical analyses conducted on serial multiplex IHC slides further revealed that only 4.87% of peritumoral immune hotspots and 0.26% of intratumoral immune hotspots were tertiary lymphoid structures. Significantly lower densities of CD20+CXCR5+ and CD79b+ B cells and less diverse immune cell interactions were found in intratumoral immune hotspots compared with peritumoral immune hotspots. Furthermore, there was a negative correlation between the percentages of CD8+ T cells and T regulatory cells in intratumoral but not in peritumoral immune hotspots, with tertiary lymphoid structures excluded. These findings suggest that the intratumoral immune hotspots reflect an immunosuppressive niche compared with peritumoral immune hotspots, independent of the distribution of tertiary lymphoid structures. A balance toward increased intratumoral immune hotspots is indicative of a compromised antitumor immune response and poor outcome in lung squamous cell carcinoma. SIGNIFICANCE: Intratumoral immune hotspots beyond tertiary lymphoid structures reflect an immunosuppressive microenvironment, different from peritumoral immune hotspots, warranting further study in the context of immunotherapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.