ArticleCancer research2012
Inhibiting systemic autophagy during interleukin 2 immunotherapy promotes long-term tumor regression.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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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.
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Who cites it
91 citing papers in PubMed, 157 citations in OpenAlex.
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- Advances in Liposomal Interleukin and Liposomal Interleukin Gene Therapy for Cancer: A Comprehensive Review of Preclinical Studies.Pharmaceutics · 2025Review
- Role of vascular endothelium and exosomes in cancer progression and therapy (Review).International journal of oncology · 2025Review
- The crosstalk of caveolin-1 and autophagy in different diseases.Frontiers in immunology · 2025Review
- Cervical Cancer Cells Use the CD95 and IL-2 Pathways to Promote Their Proliferation and Survival.Biomolecules · 2024Article
- Review
- Non-apoptotic regulated cell death mediates reprogramming of the tumour immune microenvironment by macrophages.Journal of cellular and molecular medicine · 2024Review
- Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.The Journal of pharmacology and experimental therapeutics · 2024Article
- Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders.Nature cell biology · 2024Article
- Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.Cancers · 2023Article
- Review
- Delineating the twin role of autophagy in lung cancer.Biologia futura · 2023Review
- Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer.International journal of molecular sciences · 2023Review
- LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral.Oncology research · 2023Article
- Autophagy in Cancer Immunotherapy.Cells · 2022Review
- Pentacyclic triterpenoid ursolic acid induces apoptosis with mitochondrial dysfunction in adult T-cell leukemia MT-4 cells to promote surrounding cell growth.Medical oncology (Northwood, London, England) · 2022Article
- Chimeric Peptides/Proteins Encoded by circRNA: An Update on Mechanisms and Functions in Human Cancers.Frontiers in oncology · 2022Review
- Lucanthone Targets Lysosomes to Perturb Glioma Proliferation, Chemoresistance and Stemness, and Slows Tumor GrowthFrontiers in oncology · 2022Article
- Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers.Cancers · 2021Review
31 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
11 authors at 1 institution in 1 country.
Funding
Abstract
Administration of high-dose interleukin-2 (HDIL-2) has durable antitumor effects in 5% to 10% of patients with melanoma and renal cell carcinoma. However, treatment is often limited by side effects, including reversible, multiorgan dysfunction characterized by a cytokine-induced systemic autophagic syndrome. Here, we hypothesized that the autophagy inhibitor chloroquine would enhance IL-2 immunotherapeutic efficacy and limit toxicity. In an advanced murine metastatic liver tumor model, IL-2 inhibited tumor growth in a dose-dependent fashion. These antitumor effects were significantly enhanced upon addition of chloroquine. The combination of IL-2 with chloroquine increased long-term survival, decreased toxicity associated with vascular leakage, and enhanced immune cell proliferation and infiltration in the liver and spleen. HDIL-2 alone increased serum levels of HMGB1, IFN-γ, IL-6, and IL-18 and also induced autophagy within the liver and translocation of HMGB1 from the nucleus to the cytosol in hepatocytes, effects that were inhibited by combined administration with chloroquine. In tumor cells, chloroquine increased autophagic vacuoles and LC3-II levels inhibited oxidative phosphorylation and ATP production and promoted apoptosis, which was associated with increased Annexin-V(+)/propidium iodide (PI)(-) cells, cleaved PARP, cleaved caspase-3, and cytochrome c release from mitochondria. Taken together, our findings provide a novel clinical strategy to enhance the efficacy of HDIL-2 immunotherapy for patients with cancer.
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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.