ArticleThe Journal of clinical investigation2019
The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 110 citations in OpenAlex.
- Resveratrol derivative restores macrophage cholesterol homeostasis via stabilizing xanthine oxidoreductase in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- MyD88-mediated chimaeric antigen receptor macrophages suppress brain metastasis using target-specific phagocytosis.Nature biomedical engineering · 2026Article
- Neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin for locally advanced, resectable esophageal squamous cell carcinoma: clinical study and mechanistic exploration.NPJ precision oncology · 2026Article
- Immune exhaustion in esophageal cancer: interferon pathway dysregulation and neoadjuvant therapy response.Frontiers in cell and developmental biology · 2026Review
- RNF213 governs divergent tumor-immune dynamics across human cancers: a prognostic biomarker for immunotherapy stratification.Discover oncology · 2025Article
- Mechanisms of breast cancer metastasis: the role of extracellular matrix.Molecular and cellular biochemistry · 2025Review
- Unravelling the role of ubiquitin-specific proteases in breast carcinoma: insights into tumour progression and immune microenvironment modulation.World journal of surgical oncology · 2025Review
- NF-κB associated markers of prognosis in early and metastatic triple negative breast cancer.Breast cancer research : BCR · 2024Article
- The roles of PD-L1 in the various stages of tumor metastasis.Cancer metastasis reviews · 2024Review
- Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.Molecular cancer · 2024Article
- The role of programmed death receptor (PD-)1/PD-ligand (L)1 in periodontitis and cancer.Periodontology 2000 · 2024Review
- Caspase-4 promotes metastasis and interferon-γ-induced pyroptosis in lung adenocarcinoma.Communications biology · 2024Article
- Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced non-small-cell lung cancer.Journal for immunotherapy of cancer · 2024Article
- miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression.Nature communications · 2024Article
- Phenotypic Heterogeneity, Bidirectionality, Universal Cues, Plasticity, Mechanics, and the Tumor Microenvironment Drive Cancer Metastasis.Biomolecules · 2024Review
- Effects of Metformin on JNK Signaling Pathway and PD-L1 Expression in Triple Negative Breast Cancer.Cancer management and research · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PD-L1 is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1+ tumors, as well as their roles in determining therapeutic efficacies are unknown. Here we identified, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent IFN-γ signature and potentially signified pro-inflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-κB signal elicited by macrophage inflammatory responses generated PD-L1+ cancer cells exhibiting capabilities to aggressively survive, support angiogenesis, and metastasize, whereas STAT1 signal triggered by activated T cells induced PD-L1+ cancer cells susceptive to apoptosis. Importantly, PD-L1+ cancer cells generated by macrophages established great resistance to conventional chemotherapy, cytotoxicity of tumor-specific effector T cells, and therapy of immune checkpoint blockade. Therapeutic strategy combining immune checkpoint blockade with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited caner regression. Our results provide insight into the functional features of PD-L1+ tumors and suggest that strategies to influence functional activities of inflammatory cells may benefit immune checkpoint blockade therapy.
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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 OpenQuestion graph.