ArticleJCI insight2018
TSC2-deficient tumors have evidence of T cell exhaustion and respond to anti-PD-1/anti-CTLA-4 immunotherapy.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Complete response to dual immune checkpoint blockade in a patient with Birt-Hogg-Dubé syndrome and epithelioid angiomyolipoma.Journal for immunotherapy of cancer · 2026Article
- Exploring the Role of Neutrophils in Pathogenesis of Lymphangioleiomyomatosis.Journal of innate immunity · 2026Review
- Mitochondrial metabolic rewiring sensitizes mTORC1 inhibitor persister cells to cuproptosis.JCI insight · 2025Article
- Modulation of infiltrating CD206The European respiratory journal · 2025Article
- mTOR dysregulation induces IL-6 and paracrine AT2 cell senescence impeding lung repair in lymphangioleiomyomatosis.Nature communications · 2025Article
- Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence.Oncotarget · 2025Article
- Novel treatment strategies for lymphangioleiomyomatosis: a narrative review.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- Exceptional Response in a Patient with mRCC Through Precision-Guided Treatment Involving Immunotherapy Rechallenge with Temsirolimus and Bevacizumab.Journal of immunotherapy and precision oncology · 2025Article
- Continuous response to maintenance fuzuloparib for germline BRCA2- mutated metastatic pancreatic adenocarcinoma: a case report and literature review.Frontiers in pharmacology · 2025Article
- Benign tumors broaden the field of application for immunotherapy.Frontiers in immunology · 2025Review
- STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- The development for emerging biomarkers of lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2024Review
- Plasmacytoid Dendritic Cells Mediate CpG-ODN-induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- Plasmacytoid Dendritic Cells: Bring a Glimmer of Hope for Patients with Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- CD8Frontiers in immunology · 2024Review
- Lymphangioleiomyomatosis: where endocrinology, immunology and tumor biology meet.Endocrine-related cancer · 2023Review
- Induction by rapamycin and proliferation‑promoting activity of Hspb1 in aExperimental and therapeutic medicine · 2023Article
- Lymphangioleiomyomatosis and Other Cystic Lung Diseases.Immunology and allergy clinics of North America · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Tuberous sclerosis complex (TSC) is an incurable multisystem disease characterized by mTORC1-hyperactive tumors. TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer. Whether TSC-associated tumors will respond to immunotherapy is unknown. We report here that the programmed death 1 coinhibitory receptor (PD-1) is upregulated on T cells in renal angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM). In C57BL/6J mice injected with syngeneic TSC2-deficient cells, anti-PD-1 alone decreased 105K tumor growth by 67% (P < 0.0001); the combination of PD-1 and CTLA-4 blockade was even more effective in suppressing tumor growth. Anti-PD-1 induced complete rejection of TSC2-deficient 105K tumors in 37% of mice (P < 0.05). Double blockade of PD-1 and CTLA-4 induced rejection in 62% of mice (P < 0.01). TSC2 reexpression in TSC2-deficient TMKOC cells enhanced antitumor immunity by increasing T cell infiltration and production of IFN-γ/TNF-α by T cells, suggesting that TSC2 and mTORC1 play specific roles in the induction of antitumor immunity. Finally, 1 month of anti-PD-1 blockade reduced renal tumor burden by 53% (P < 0.01) in genetically engineered Tsc2+/- mice. Taken together, these data demonstrate for the first time to our knowledge that checkpoint blockade may have clinical efficacy for TSC and LAM, and possibly other benign tumor syndromes, potentially yielding complete and durable clinical responses.
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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.