ArticleCell communication and signaling : CCS2022
Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Global research trends on macrophage polarization in osteoarthritis: a bibliometric analysis.Frontiers in immunology · 2025Pooled it
- The Unfolded Protein Response as a Modulator of Cancer-Immune Cell Communication in the Tumour Microenvironment.Journal of cellular and molecular medicine · 2026Review
- From signals to phenotype: multifactorial drivers of tumor-associated macrophage polarization in oral cavity squamous cell carcinoma: a narrative review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Review
- Extracellular Vesicles in Head and Neck Cancer-A Systematic Review.Journal of extracellular biology · 2026Review
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.Cancer cell international · 2025Review
- Dual-locked targeted alpha-emitter enhanced tumor immunotherapy via Diels-Alder reaction-based self-immolative molecular cage strategy.Military Medical Research · 2025Article
- ATF6 and pS6K as prognostic biomarkers in newly diagnosed diffuse large B-cell lymphoma.Scientific reports · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Exosomes as Central Mediators of Host-Pathogen Interactions in Periodontitis: A Systematic Literature Review.Cureus · 2025Review
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Piperlongumine Inhibits Lung Cancer Growth by Inducing Endoplasmic Reticulum Stress Leading to Suppression of M2 Macrophage Polarization.Biological procedures online · 2025Article
- ATF6 activation promotes tumorigenesis and drug resistance in diffuse large B-cell lymphoma (DLBCL) by regulating the mTOR/S6K signaling pathway.Discover oncology · 2025Article
- Cancer ATF4-mediated CD58 endocytosis impairs anti-tumor immunity and immunotherapy.Journal of translational medicine · 2025Article
- Emerging roles of extracellular vesicles in oral and maxillofacial areas.International journal of oral science · 2025Review
- STC1 encapsulated in small extracellular vesicles from laryngeal squamous cell carcinoma cells induces CD8Cancer immunology, immunotherapy : CII · 2025Article
- Identification of an anti-inflammatory action of exosome release in P2YFrontiers in pharmacology · 2025Article
- Exosomal PD-L1 detection in cancer predictive biomarker for response to immune checkpoint blockade therapy.Frontiers in immunology · 2025Review
- Decoding the Tumor Microenvironment: Exosome-Mediated Macrophage Polarization and Therapeutic Frontiers.International journal of biological sciences · 2025Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEndoplasmic reticulum (ER) stress has been found to foster the escape of cancer cells from immune surveillance and upregulate PD-L1 expression. However, the underlying mechanisms are unknown.
methodsWhile analyzing the protein levels using immunofluorescence and Western blotting, the RNA levels were measured using qRT-PCR. Ten injection of exosomes into six-week-old nude mice was made through the tail vein once every other day in total.
resultsThe expression of certain ER stress markers such as PERK (PKR-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6), and GRP78 (glucose-regulated protein 78), was found to be upregulated in the oral squamous cell carcinoma (OSCC) tissues and related to poor overall survival. There is a positive relationship between the extent of ER stress-related proteins and a cluster of PD-L1 expression and macrophage infiltration among the OSCC tissues. Further, incubation with exosomes derived from ER-stressed HN4 cells (Exo-ER) was found to upregulate PD-L1 extents in macrophages in vitro and in vivo, and macrophage polarization toward the M2 subtype was promoted by upregulating PD-L1.
conclusionsER stress causes OSCC cells to secrete exosomal PD-L1 and upregulates PD-L1 expression in macrophages to drive M2 macrophage polarization. The delineation of a new exosome-modulated mechanism was made for OSCC-macrophage crosstalk driving tumor development and to be examined for its therapeutic use. Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization. Video Abstract.
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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.