ArticleCell death and differentiation2014
Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 98 citations in OpenAlex.
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- NAMPT inhibition induces ferroptosis via mitochondrial metabolic reprogramming to enhance tumour immunogenicity in glioblastoma.Frontiers in immunology · 2026Article
- How macrophages use extracellular calreticulin to chase their prey.Oncoimmunology · 2025Article
- FGD3 mediates lytic cell death, enhancing efficacy and immunogenicity of chemotherapy agents in breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Polyinosinic/Polycytidylic Lipid Nanoparticles Enhance Immune Cell Infiltration and Improve Survival in the Glioblastoma Mouse Model.Molecular pharmaceutics · 2024Article
- Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death.Nature communications · 2024Article
- Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.Biomarker research · 2024Article
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- Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.Journal of Cancer · 2024Review
- Elevated Nuclear PHGDH Synergistically Functions with cMyc to Reshape the Immune Microenvironment of Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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- Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity.Nature communications · 2022Article
- Immunogenic cell stress and death.Nature immunology · 2022Review
- Stress-induced inflammation evoked by immunogenic cell death is blunted by the IRE1α kinase inhibitor KIRA6 through HSP60 targeting.Cell death and differentiation · 2022Article
- The Strategies and Mechanisms of Immune Checkpoint Inhibitors for Brain Metastases in NSCLC.Frontiers in pharmacology · 2022Review
- Conventional amphotericin B elicits markers of immunogenic cell death on leukemic blasts, mediates immunostimulatory effects on phagocytic cells, and synergizes with PD-L1 blockade.Oncoimmunology · 2022Article
- Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity.Oncoimmunology · 2022Article
- Identification of prognostic and therapeutic value of CC chemokines in Urothelial bladder cancer: evidence from comprehensive bioinformatic analysis.BMC urology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
The exposure of calreticulin (CRT) on the surface of stressed and dying cancer cells facilitates their uptake by dendritic cells and the subsequent presentation of tumor-associated antigens to T lymphocytes, hence stimulating an anticancer immune response. The chemotherapeutic agent mitoxantrone (MTX) can stimulate the peripheral relocation of CRT in both human and yeast cells, suggesting that the CRT exposure pathway is phylogenetically conserved. Here, we show that pheromones can act as physiological inducers of CRT exposure in yeast cells, thereby facilitating the formation of mating conjugates, and that a large-spectrum inhibitor of G protein-coupled receptors (which resemble the yeast pheromone receptor) prevents CRT exposure in human cancer cells exposed to MTX. An RNA interference screen as well as transcriptome analyses revealed that chemokines, in particular human CXCL8 (best known as interleukin-8) and its mouse ortholog Cxcl2, are involved in the immunogenic translocation of CRT to the outer leaflet of the plasma membrane. MTX stimulated the production of CXCL8 by human cancer cells in vitro and that of Cxcl2 by murine tumors in vivo. The knockdown of CXCL8/Cxcl2 receptors (CXCR1/Cxcr1 and Cxcr2) reduced MTX-induced CRT exposure in both human and murine cancer cells, as well as the capacity of the latter-on exposure to MTX-to elicit an anticancer immune response in vivo. Conversely, the addition of exogenous Cxcl2 increased the immunogenicity of dying cells in a CRT-dependent manner. Altogether, these results identify autocrine and paracrine chemokine signaling circuitries that modulate CRT exposure and the immunogenicity of cell death.
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Registered trials
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