ArticleJournal for immunotherapy of cancer2019
Proliferative potential and resistance to immune checkpoint blockade in lung cancer patients.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- The landscape of objective response rate of anti-PD-1/L1 monotherapy across 31 types of cancer: a system review and novel biomarker investigating.Cancer immunology, immunotherapy : CII · 2023Pooled it
- Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition.Cell · 2021Pooled it
- Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.Nature medicine · 2025Trial
- Deep learning multi-omics integration identifies new molecular subtypes of lung cancer.BioData mining · 2026Article
- Directions of Immunotherapy for Non-Small-Cell Lung Cancer Treatment: Past, Present and Possible Future.International journal of molecular sciences · 2025Review
- Single-cell RNA profiling reveals an immunosuppressive microenvironment inTranslational lung cancer research · 2025Article
- Distinct molecular subtypes of KRASClinical and translational medicine · 2025Article
- Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma.Nature communications · 2025Article
- Transcriptomic and miRNA Signatures of ChAdOx1 nCoV-19 Vaccine Response Using Machine Learning.Life (Basel, Switzerland) · 2025Article
- The Role of Perirenal Adipose Tissue in Carcinogenesis-From Molecular Mechanism to Therapeutic Perspectives.Cancers · 2025Review
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Five latent factors underlie response to immunotherapy.Nature genetics · 2024Article
- Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer.Cancer cell international · 2024Article
- Human pan-cancer analysis of the predictive biomarker for the CDKN3.European journal of medical research · 2024Article
- Immunologic Factors Associated with Differential Response to Neoadjuvant Chemoimmunotherapy in Triple-Negative Breast Cancer.Journal of personalized medicine · 2024Article
- E2F1-EP300 co-activator complex potentiates immune escape in nasopharyngeal carcinoma through the mediation of MELK.Histology and histopathology · 2024Article
- A signature of enhanced proliferation associated with response and survival to anti-PD-L1 therapy in early-stage non-small cell lung cancer.Cell reports. Medicine · 2024Article
- Article
- Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer.Journal of translational medicine · 2024Article
- Spatial and temporal heterogeneity of tumor immune microenvironment between primary tumor and brain metastases in NSCLC.BMC cancer · 2024Article
Corrections and comments
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Authors and funding
46 authors at 12 institutions in 7 countries.
Funding
Abstract
backgroundResistance to immune checkpoint inhibitors (ICIs) has been linked to local immunosuppression independent of major ICI targets (e.g., PD-1). Clinical experience with response prediction based on PD-L1 expression suggests that other factors influence sensitivity to ICIs in non-small cell lung cancer (NSCLC) patients.
methodsTumor specimens from 120 NSCLC patients from 10 institutions were evaluated for PD-L1 expression by immunohistochemistry, and global proliferative profile by targeted RNA-seq.
resultsCell proliferation, derived from the mean expression of 10 proliferation-associated genes (namely BUB1, CCNB2, CDK1, CDKN3, FOXM1, KIAA0101, MAD2L1, MELK, MKI67, and TOP2A), was identified as a marker of response to ICIs in NSCLC. Poorly, moderately, and highly proliferative tumors were somewhat equally represented in NSCLC, with tumors with the highest PD-L1 expression being more frequently moderately proliferative as compared to lesser levels of PD-L1 expression. Proliferation status had an impact on survival in patients with both PD-L1 positive and negative tumors. There was a significant survival advantage for moderately proliferative tumors compared to their combined highly/poorly counterparts (p = 0.021). Moderately proliferative PD-L1 positive tumors had a median survival of 14.6 months that was almost twice that of PD-L1 negative highly/poorly proliferative at 7.6 months (p = 0.028). Median survival in moderately proliferative PD-L1 negative tumors at 12.6 months was comparable to that of highly/poorly proliferative PD-L1 positive tumors at 11.5 months, but in both instances less than that of moderately proliferative PD-L1 positive tumors. Similar to survival, proliferation status has impact on disease control (DC) in patients with both PD-L1 positive and negative tumors. Patients with moderately versus those with poorly or highly proliferative tumors have a superior DC rate when combined with any classification schema used to score PD-L1 as a positive result (i.e., TPS ≥ 50% or ≥ 1%), and best displayed by a DC rate for moderately proliferative tumors of no less than 40% for any classification of PD-L1 as a negative result. While there is an over representation of moderately proliferative tumors as PD-L1 expression increases this does not account for the improved survival or higher disease control rates seen in PD-L1 negative tumors.
conclusionsCell proliferation is potentially a new biomarker of response to ICIs in NSCLC and is applicable to PD-L1 negative tumors.
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