ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Novel Lymphocyte-Independent Antitumor Activity by PD-1 Blocking Antibody against PD-1+ Chemoresistant Lung Cancer Cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial.Nature medicine · 2024Trial
- Nivolumab Enhances the Cytotoxicity of Chemotherapeutic Agents in A549 Lung Adenocarcinoma Cell Lines.Current issues in molecular biology · 2026Article
- Survivin/BIRC5-derived peptide disrupts survivin dimerization and cell division and induces multifaceted anti-cancer effects.Molecular therapy. Oncology · 2026Article
- Tumor cell-intrinsic PD-1 regulates chemotherapy resistance in colorectal cancer cells by activating downstream MAPK signaling.BJC reports · 2025Article
- Decoding cancer dormancy: integrative genomic, phenotypic and live-cell imaging analysis to reveal the hidden cancer cell reservoir.Molecular cancer · 2025Review
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- Programmed cell death protein 1 in cancer cells.Cell communication and signaling : CCS · 2025Review
- Unlocking the mystery of the PD-1/PD-L1 axis: beyond the checkpoint hype.Frontiers in immunology · 2025Review
- PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs.Cell communication and signaling : CCS · 2024Article
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- PD-1 expression on tumor cells: a new target for cancer therapy.Translational lung cancer research · 2024Article
- Current status of molecular diagnostics for lung cancer.Exploration of targeted anti-tumor therapy · 2024Review
- PD-1 receptor outside the main paradigm: tumour-intrinsic role and clinical implications for checkpoint blockade.British journal of cancer · 2023Review
- Old Dog, New Trick: A Tumor-Intrinsic Role for PD-1 in Chemoresistant Tumor Subclones.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
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30 authors at 8 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
purposeAntibodies against the lymphocyte PD-1 (aPD-1) receptor are cornerstone agents for advanced non-small cell lung cancer (NSCLC), based on their ability to restore the exhausted antitumor immune response. Our study reports a novel, lymphocyte-independent, therapeutic activity of aPD-1 against NSCLC, blocking the tumor-intrinsic PD-1 receptors on chemoresistant cells. EXPERIMENTAL
designPD-1 in NSCLC cells was explored in vitro at baseline, including stem-like pneumospheres, and following treatment with cisplatin both at transcriptional and protein levels. PD-1 signaling and RNA sequencing were assessed. The lymphocyte-independent antitumor activity of aPD-1 was explored in vitro, by PD-1 blockade and stimulation with soluble ligand (PD-L1s), and in vivo within NSCLC xenograft models.
resultsWe showed the existence of PD-1+ NSCLC cell subsets in cell lines and large in silico datasets (Cancer Cell Line Encyclopedia and The Cancer Genome Atlas). Cisplatin significantly increased PD-1 expression on chemo-surviving NSCLC cells (2.5-fold P = 0.0014), while the sequential treatment with anti-PD-1 Ab impaired their recovery after chemotherapy. PD-1 was found to be associated with tumor stemness features. PD-1 expression was enhanced in NSCLC stem-like pneumospheres (P < 0.0001), significantly promoted by stimulation with soluble PD-L1 (+27% ± 4, P < 0.0001) and inhibited by PD-1 blockade (-30% ± 3, P < 0.0001). The intravenous monotherapy with anti-PD-1 significantly inhibited tumor growth of NSCLC xenografts in immunodeficient mice, without the contribution of the immune system, and delayed the occurrence of chemoresistance when combined with cisplatin.
conclusionsWe report first evidence of a novel lymphocyte-independent activity of anti-PD-1 antibodies in NSCLC, capable of inhibiting chemo-surviving NSCLC cells and exploitable to contrast disease relapses following chemotherapy. See related commentary by Augustin et al., p. 505.
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