CD57-positive CD8 + T cells define the response to anti-programmed cell death protein-1 immunotherapy in patients with advanced non-small cell lung cancer

Immune checkpoint inhibitors have transformed the treatment landscape of non-small cell lung cancer (NSCLC). However, accurately identifying patients who will benefit from immunotherapy remains a challenge. This study aimed to discover potential biomarkers for predicting immunotherapy response in NSCLC patients. Single-cell mass cytometry (CyTOF) was utilized to analyze immune cell subsets in peripheral blood mononuclear cells (PBMCs) obtained from NSCLC patients before and 12 weeks after single-agent immunotherapy. The CyTOF findings were subsequently validated using flow cytometry and multiplex immunohistochemistry/immunofluorescence in PBMCs and tumor tissues, respectively. RNA sequencing (RNA-seq) was performed to elucidate the underlying mechanisms. In the CyTOF cohort (n = 20), a high frequency of CD57+CD8+ T cells in PBMCs was associated with durable clinical benefit from immunotherapy in NSCLC patients (p = 0.034). This association was further confirmed in an independent cohort using flow cytometry (n = 27; p < 0.001), with a determined cutoff value of 12.85%. The cutoff value was subsequently validated in another independent cohort (AUC = 0.733). We also confirmed the CyTOF findings in pre-treatment formalin-fixed and paraffin-embedded tissues (n = 90; p < 0.001). RNA-seq analysis revealed 475 differentially expressed genes (DEGs) between CD57+CD8+ T cells and CD57-CD8+ T cells, with functional analysis identifying DEGs significantly enriched in immune-related signaling pathways. This study highlights CD57+CD8+ T cells as a promising biomarker for predicting immunotherapy success in NSCLC patients.

• Publication year

  2024

• Venue

  npj Precision Oncology

• Publication date

  2024-01-31

• Fields of study

  Medicine

• Identifiers
  DOI 10.1038/s41698-024-00513-0PMID 38297019PMCID 10830454
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Molecular profiling of human non-small cell lung cancer by single-cell RNA-seq

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• Identification of a cytokine-dominated immunosuppressive class in squamous cell lung carcinoma with implications for immunotherapy resistance

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• T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors

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• TMB in NSCLC: A Broken Dream?

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• Intra-tumoral CD39+CD8+ T cells predict response to PD-1/PD-L1 blockade in patients with NSCLC.

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• Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer

  2021cited by this paper
• A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy.

  2021cited by this paper
• Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer

  2020cited by this paper
• Efficacy and safety of immune checkpoint inhibitors in patients with advanced non–small cell lung cancer (NSCLC): a systematic literature review

  2020cited by this paper
• Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies

  2020cited by this paper
• CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer

  2020cited by this paper
• Acquired Resistance to Immune Checkpoint Inhibitors.

  2020cited by this paper
• Tumor mutational load, CD8+ T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients

  2020cited by this paper
• Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy

  2019influential reference
• CD45RA+CCR7− CD8 T cells lacking co-stimulatory receptors demonstrate enhanced frequency in peripheral blood of NSCLC patients responding to nivolumab

  2019cited by this paper
• Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

  2019cited by this paper
• Prognostic and predictive role of CD8 and PD-L1 determination in lung tumor tissue of patients under anti-PD-1 therapy

  2018cited by this paper
• The Gene Ontology Resource: 20 years and still GOing strong

  2018influential reference
• High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy

  2018cited by this paper
• The anatomy of single cell mass cytometry data

  2018cited by this paper
• Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden

  2018cited by this paper
• Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA

  2018cited by this paper
• fastp: an ultra-fast all-in-one FASTQ preprocessor

  2018cited by this paper
• First-Line Nivolumab in Stage IV or Recurrent Non-Small Cell Lung Cancer

  2017cited by this paper
• First‐Line Nivolumab in Stage IV or Recurrent Non–Small‐Cell Lung Cancer

  2017cited by this paper
• Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).

  2017cited by this paper
• Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.

  2016cited by this paper
• Automated Mapping of Phenotype Space with Single-Cell Data

  2016cited by this paper
• Prognostic role of tumor-infiltrating CD57-positive lymphocytes in solid tumors: a meta-analysis

  2015cited by this paper
• Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.

  2015cited by this paper
• Pembrolizumab for the treatment of non-small-cell lung cancer.

  2015cited by this paper
• HISAT: a fast spliced aligner with low memory requirements

  2015cited by this paper
• Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

  2014cited by this paper
• Different subsets of natural killer T cells may vary in their roles in health and disease

  2014cited by this paper
• HTSeq—a Python framework to work with high-throughput sequencing data

  2014cited by this paper
• Normalization of mass cytometry data with bead standards

  2013cited by this paper
• Improving RNA-Seq expression estimates by correcting for fragment bias

  2011cited by this paper
• Combination therapy of in vitro‐expanded natural killer T cells and α‐galactosylceramide‐pulsed antigen‐presenting cells in patients with recurrent head and neck carcinoma

  2009cited by this paper
• Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE.

  2009cited by this paper
• KEGG for linking genomes to life and the environment

  2007influential reference
• From the Cover: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

  2005cited by this paper
• Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells.

  2003cited by this paper
• PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes

  2003cited by this paper

• Peripheral Immune Biomarkers Associated with Response to Adoptive Cell Therapy with Tumor Infiltrating Lymphocytes.

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• Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment

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• Research progress on photoelectrochemical immunosensors for serum markers of thoracic malignancy: A review

  2025cites this paper
• A phase 2 trial of CXCR4 antagonism and PD1 inhibition in metastatic pancreatic adenocarcinoma reveals recruitment of T cells but also immunosuppressive macrophages

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• Pan-cancer convergence of tumour–immune microenvironment motifs revealed by CyTOF and imaging mass cytometry

  2025cites this paper
• Profiling of circulating T-cells with prognostic and predictive value in early and advanced stage PDAC

  2025cites this paper
• Re-evaluating CD57 as a marker of T cell senescence: implications for immune ageing and differentiation

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• CD2 costimulation strength: A key regulator of T cell function and anti-tumor immunity that is epigenetically regulated

  2025cites this paper