ArticleOncotarget2017
Unfolded protein response signaling impacts macrophage polarity to modulate breast cancer cell clearance and melanoma immune checkpoint therapy responsiveness.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Murine Models of Obesity-Related Cancer Risk.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Dietary influences on chemotherapy sensitivity and cardiotoxicity modulated by IRE1 targeting in triple-negative breast cancer in female mice.Physiological reports · 2025Article
- Review
- Review
- A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer.Journal of Zhejiang University. Science. B · 2023Article
- Endoplasmic reticulum stress targeted therapy for breast cancer.Cell communication and signaling : CCS · 2022Review
- Epigenomic and transcriptomic analyses reveal differences between low-grade inflammation and severe exhaustion in LPS-challenged murine monocytes.Communications biology · 2022Article
- Deletion of ACLY Disrupts Histone Acetylation and IL-10 Secretion in Trophoblasts, Which Inhibits M2 Polarization of Macrophages: A Possible Role in Recurrent Spontaneous Abortion.Oxidative medicine and cellular longevity · 2022Article
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- GRP78 facilitates M2 macrophage polarization and tumour progression.Cellular and molecular life sciences : CMLS · 2021Article
- The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis.Cancers · 2021Review
- CCL23 in Balancing the Act of Endoplasmic Reticulum Stress and Antitumor Immunity in Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Inhibiting P2Y12 in Macrophages Induces Endoplasmic Reticulum Stress and Promotes an Anti-Tumoral Phenotype.International journal of molecular sciences · 2020Article
- Article
- KSHV infection skews macrophage polarisation towards M2-like/TAM and activates Ire1 α-XBP1 axis up-regulating pro-tumorigenic cytokine release and PD-L1 expression.British journal of cancer · 2020Article
- Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response.International journal of molecular sciences · 2019Review
- Structure-based design generated novel hydroxamic acid based preferential HDAC6 lead inhibitor with on-target cytotoxic activity against primary choroid plexus carcinoma.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Endoplasmic reticulum stress enhances the antigen-specific T cell immune responses and therapeutic antitumor effects generated by therapeutic HPV vaccines.Journal of biomedical science · 2019Article
- IL-6 mediates ER expansion during hyperpolarization of alternatively activated macrophages.Immunology and cell biology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The unfolded protein response (UPR) is a stress pathway controlled by GRP78 to mediate IRE1, PERK, and ATF6 signaling. We show that targeting GRP78, IRE1, and PERK differentially regulates macrophage polarization. Specifically, PERK targeting enhanced macrophage proliferation and macrophage-mediated killing but not GRP78 or IRE1. Targeting UPR in cancer cells also differentially affected macrophage cytolytic capacity. Tumoral IRE1 or GRP78 inhibition enhanced macrophage-mediated cancer cell clearance. Conditioned media from GRP78-silenced cancer cells caused reciprocal regulation of CD80 and CD206, suggesting control of plasticity by secreted factors. GRP78 targeting in mice resulted in a cytokine shift and increased tumoral CD80+/CD68+ cells, suggesting an M1-like profile. Targeting UPR in both macrophage and cancer cells indicates that PERK or GRP78 reduction enhances macrophage clearance of cancer cells. Recent evidence suggests that macrophage polarization influences immune checkpoint therapy resistance. To determine whether UPR effects immunotherapy resistance, analysis of matched melanoma patient PBMC before/after developing ipilimumab resistance demonstrated increased UPR signaling and an M2-like macrophage population, supporting a novel role of UPR signaling and innate immune regulation in anti-CTLA-4 therapy resistance. These data suggest that targeting GRP78 or PERK promotes an anti-tumor immune response by either directly promoting macrophage cytolytic activity or indirectly by shifting tumoral cytokine secretion.
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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.