ArticleJournal of experimental & clinical cancer research : CR2022
Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- mRNA markers for survival prediction in glioblastoma multiforme patients: a systematic review with bioinformatic analyses.BMC cancer · 2024Pooled it
- Review
- Targeting Autophagy to Overcome Chemoresistance and Immune Resistance in Triple-Negative Breast Cancer.Cancers · 2026Review
- RFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy.Nature communications · 2026Article
- The CHI3L1 protein plays role as a protecting factor against autophagy in glioblastoma cells.Apoptosis : an international journal on programmed cell death · 2026Article
- Icaritin eliminates tumor-associated macrophages via STX16-dependent extracellular vesicle delivery of autophagosomes from hepatocellular carcinoma cells.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting mesenchymal monocyte-derived macrophages to enhance the sensitivity of glioblastoma to temozolomide by inhibiting TNF/CELSR2/p65/Kla-HDAC1/EPAS1 axis.Journal of advanced research · 2026Article
- Antiatopic dermatitis activity ofTurkish journal of biology = Turk biyoloji dergisi · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Spatiotemporal control of immunogenic cell death: rewiring tumor-immune dialogues for next-generation immunotherapy.Frontiers in immunology · 2026Review
- Macrophage-based therapeutic strategies in glioblastoma: advancements in drug delivery and immunotherapy.Frontiers in oncology · 2026Review
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- Autophagy-dependent secretion of ENO1 mediates chemoresistance of glioblastoma and tumor microenvironment remodeling.Cell death & disease · 2025Article
- Liposomal honokiol enhance the anti-tumor effect of bevacizumab in glioblastoma by inhibiting autophagy.Future science OA · 2025Article
- Innate Immune Signaling in Gliomas: Regulatory Mechanisms and Targeting Potential in Tumor Progression.Life (Basel, Switzerland) · 2025Review
- Review: Progress of the NLRP3 inflammasome in tumours and perspectives for cholangiocarcinoma.Cell communication and signaling : CCS · 2025Review
- The HMGB1-RAGE Axis Drives the Proneural-to-Mesenchymal Transition and Aggressiveness in Glioblastoma.International journal of molecular sciences · 2025Article
- Chemoradiation-Altered Micromilieu of Glioblastoma Cells Particularly Impacts M1-like Macrophage Activation.International journal of molecular sciences · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Glioblastoma-associated macrophages in glioblastoma: from their function and mechanism to therapeutic advances.Cancer gene therapy · 2025Review
2 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
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth and resistance to alkylating chemotherapy. Autophagy induction is one of the hallmark effects of anti-GB therapies with temozolomide (TMZ). However, the non-classical form of autophagy, autophagy-based unconventional secretion, also called secretory autophagy and its role in regulating the sensitivity of GB to TMZ remains unclear. There is an urgent need to illuminate the mechanism and to develop novel therapeutic targets for GB.
methodsCancer genome databases and paired-GB patient samples with or without TMZ treatment were used to assess the relationship between HMGB1 mRNA levels and overall patient survival. The relationship between HMGB1 protein level and TMZ sensitivity was measured by immunohistochemistry, ELISA, Western blot and qRT-PCR. GB cells were engineered to express a chimeric autophagic flux reporter protein consisting of mCherry, GFP and LC3B. The role of secretory autophagy in tumor microenvironment (TME) was analyzed by intracranial implantation of GL261 cells. Coimmunoprecipitation (Co-IP) and Western blotting were performed to test the RAGE-NFκB-NLRP3 inflammasome pathway.
resultsThe exocytosis of HMGB1 induced by TMZ in GB is dependent on the secretory autophagy. HMGB1 contributed to M1-like polarization of tumor associated macrophages (TAMs) and enhanced the sensitivity of GB cells to TMZ. Mechanistically, RAGE acted as a receptor for HMGB1 in TAMs and through RAGE-NFκB-NLRP3 inflammasome pathway, HMGB1 enhanced M1-like polarization of TAMs. Clinically, the elevated level of HMGB1 in sera may serve as a beneficial therapeutic-predictor for GB patients under TMZ treatment.
conclusionsWe demonstrated that enhanced secretory autophagy in GB facilitates M1-like polarization of TAMs to enhance TMZ sensitivity of GB cells. HMGB1 acts as a key regulator in the crosstalk between GB cells and tumor-suppressive M1-like TAMs in GB microenvironment and may be considered as an adjuvant for the chemotherapeutic agent TMZ.
Indexed as
Identifiers
What OpenQuestion holds
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.