ArticleScience advances2024
Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Tumor cell-intrinsic PD-1 in malignant ascites drives ovarian cancer progression via MAPK/ERK signaling.Oncogene · 2026Article
- Tumor-Intrinsic PD-1 Regulatory Network Drives Lapatinib Resistance in HER2⁺ Breast Cancer: An Integrative Bioinformatics Analysis.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation.The British journal of dermatology · 2026Article
- Identification and Validation of Mitophagy-Related Biomarkers in Colorectal Cancer: An Integrated Analysis of Single-Cell Transcriptome and Mendelian Randomization.Genetics research · 2026Article
- Article
- Targeting the tumor cell-intrinsic ITGB2 axis inhibits melanoma progression.Molecular cancer · 2025Article
- Tumor cell-intrinsic PD-1 regulates chemotherapy resistance in colorectal cancer cells by activating downstream MAPK signaling.BJC reports · 2025Article
- Merkel cell carcinoma in solid organ transplant recipients: prognosis and response to immunotherapy.The British journal of dermatology · 2025Article
- Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression.Antioxidants (Basel, Switzerland) · 2025Review
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- Programmed cell death protein 1 in cancer cells.Cell communication and signaling : CCS · 2025Review
- Understanding Merkel Cell Carcinoma: Pathogenic Signaling, Extracellular Matrix Dynamics, and Novel Treatment Approaches.Cancers · 2025Review
- Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric cancer.World journal of gastrointestinal oncology · 2025Article
- Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment.Frontiers in immunology · 2025Review
- Exploring the differential functions of circulating follicular helper T and peripheral helper T cells in rheumatoid arthritis based on metabolism patterns.Frontiers in immunology · 2025Article
- Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.Nature communications · 2024Article
- Tumor glucose metabolism and the T cell glycocalyx: implication for T cell function.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Inhibitors targeting the programmed cell death 1 (PD-1) immune checkpoint have improved MCC patient outcomes by boosting antitumor T cell immunity. Here, we identify PD-1 as a growth-promoting receptor intrinsic to MCC cells. In human MCC lines and clinical tumors, RT-PCR-based sequencing, immunoblotting, flow cytometry, and immunofluorescence analyses demonstrated PD-1 gene and protein expression by MCC cells. MCC-PD-1 ligation enhanced, and its inhibition or silencing suppressed, in vitro proliferation and in vivo tumor xenograft growth. Consistently, MCC-PD-1 binding to PD-L1 or PD-L2 induced, while antibody-mediated PD-1 blockade inhibited, protumorigenic mTOR signaling, mitochondrial (mt) respiration, and ROS generation. Last, pharmacologic inhibition of mTOR or mtROS reversed MCC-PD-1:PD-L1-dependent proliferation and synergized with PD-1 checkpoint blockade in suppressing tumorigenesis. Our results identify an MCC-PD-1-mTOR-mtROS axis as a tumor growth-accelerating mechanism, the blockade of which might contribute to clinical response in patients with MCC.
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Registered trials
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.