ArticleJournal of experimental & clinical cancer research : CR2021
PD-1 blockade delays tumor growth by inhibiting an intrinsic SHP2/Ras/MAPK signalling in thyroid cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Cabozantinib in combination with immune checkpoint inhibitors for renal cell carcinoma: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- ATP2C2-PLA2R1 axis underlies lipid metabolism modulation and invasion in papillary thyroid carcinoma mediated by a VGIC signature.Discover oncology · 2026Article
- Immune checkpoint blockade in cancer: current insights and future horizons.Discover oncology · 2026Review
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Immune Checkpoint Restoration as a Therapeutic Strategy to Halt Diabetes-Driven Atherosclerosis.Biology · 2025Review
- Tumor cell-intrinsic PD-1 regulates chemotherapy resistance in colorectal cancer cells by activating downstream MAPK signaling.BJC reports · 2025Article
- shRNA-based PD-1 suppression preserves memory phenotype and function of CD19-targeted CAR-T cell.Translational cancer research · 2025Article
- Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro.Scientific reports · 2025Article
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- Integrating transcriptomic and metabolomic analyses to characterize the potential function of SLC1A5 in thyroid cancer.BMC cancer · 2025Article
- Targeting SHP2 with Natural Products: Exploring Saponin-Based Allosteric Inhibitors and Their Therapeutic Potential.Current issues in molecular biology · 2025Review
- Programmed cell death protein 1 in cancer cells.Cell communication and signaling : CCS · 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
- The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer.Cancer biology & therapy · 2024Article
- PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs.Cell communication and signaling : CCS · 2024Article
- An individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma.Nature communications · 2024Article
- NanoSHP099-Targeted SHP2 Inhibition Boosts Ly6CAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- New clinical trial design in precision medicine: discovery, development and direction.Signal transduction and targeted therapy · 2024Review
- Molecular basis, potential biomarkers, and future prospects of OSCC and PD-1/PD-L1 related immunotherapy methods.Heliyon · 2024Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe programmed cell death-1 (PD-1) receptor and its ligands PD-L1 and PD-L2 are immune checkpoints that suppress anti-cancer immunity. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their activity. Recently, PD-1 expression has also been found in cancer cells. Here, we analysed expression and functions of PD-1 in thyroid cancer (TC).
methodsPD-1 expression was evaluated by immunohistochemistry on human TC samples and by RT-PCR, western blot and FACS on TC cell lines. Proliferation and migration of TC cells in culture were assessed by BrdU incorporation and Boyden chamber assays. Biochemical studies were performed by western blot, immunoprecipitation, pull-down and phosphatase assays. TC cell tumorigenicity was assessed by xenotransplants in nude mice.
resultsHuman TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 was also constitutively expressed on TC cell lines. PD-1 overexpression/stimulation promoted TC cell proliferation and migration. Accordingly, PD-1 genetic/pharmacologic inhibition caused the opposite effects. Mechanistically, PD-1 recruited the SHP2 phosphatase to the plasma membrane and potentiated its phosphatase activity. SHP2 enhanced Ras activation by dephosphorylating its inhibitory tyrosine 32, thus triggering the MAPK cascade. SHP2, BRAF and MEK were necessary for PD-1-mediated biologic functions. PD-1 inhibition decreased, while PD-1 enforced expression facilitated, TC cell xenograft growth in mice by affecting tumour cell proliferation.
conclusionsPD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the SHP2/Ras/MAPK signalling pathway.
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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 Socratic graph.