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Updated: Oct 13, 2025
Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells
Published on: May 20, 2020
Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient
Andrew M Leader1, John A Grout1, Barbara B Maier1
1The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract:
Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. While tumor mutational burden (TMB) correlates with response to immunotherapy, little is known about the relationship between the baseline immune response and tumor genotype. Using single-cell RNA sequencing, we profiled 361,929 cells from 35 early-stage NSCLC lesions. We identified a cellular module consisting of PDCD1+CXCL13+ activated T cells, IgG+ plasma cells, and SPP1+ macrophages, referred to as the lung cancer activation module (LCAMhi). We confirmed LCAMhi enrichment in multiple NSCLC cohorts, and paired CITE-seq established an antibody panel to identify LCAMhi lesions. LCAM presence was found to be independent of overall immune cell content and correlated with TMB, cancer testis antigens, and TP53 mutations. High baseline LCAM scores correlated with enhanced NSCLC response to immunotherapy even in patients with above median TMB, suggesting that immune cell composition, while correlated with TMB, may be a nonredundant biomarker of response to immunotherapy.
Insights
This study identifies a novel immune cell signature, the lung cancer activation module (LCAM), in early-stage non-small cell lung cancer (NSCLC). LCAM predicts immunotherapy response, offering a new biomarker beyond tumor mutational burden (TMB).
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immunotherapy is crucial for non-small cell lung cancer (NSCLC) treatment.
- Tumor mutational burden (TMB) predicts response, but baseline immune-genomic interactions are unclear.
Purpose of the Study:
- To investigate the relationship between baseline immune response and tumor genotype in early-stage NSCLC.
- To identify novel biomarkers for predicting immunotherapy response in NSCLC.
Main Methods:
- Single-cell RNA sequencing of 361,929 cells from 35 early-stage NSCLC lesions.
- Identification and validation of the lung cancer activation module (LCAM) using CITE-seq.
- Analysis of LCAM correlation with TMB, cancer testis antigens, and TP53 mutations.
Main Results:
- A distinct cellular module, LCAM (PDCD1+CXCL13+ T cells, IgG+ plasma cells, SPP1+ macrophages), was identified.
- LCAM enrichment was confirmed across NSCLC cohorts and is independent of overall immune cell content.
- LCAM correlated with TMB, cancer testis antigens, and TP53 mutations.
Conclusions:
- High baseline LCAM scores predict enhanced NSCLC response to immunotherapy, even with high TMB.
- Immune cell composition, indicated by LCAM, serves as a non-redundant biomarker for immunotherapy response in NSCLC.
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