ArticleJCI insight2023
Overcoming lung cancer immunotherapy resistance by combining nontoxic variants of IL-12 and IL-2.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Endobronchial Intratumoral Immuno- and Gene Therapies in Lung Cancer: Mechanisms of Local Delivery, Systemic Immune Effects, and Global Feasibility.International journal of molecular sciences · 2026Review
- Importance of the delivery route for the tolerability and efficacy of immunomodulatory agents for lung cancer.Scientific reports · 2026Article
- Rewiring tumor cytokine networks to enhance immune checkpoint blockade: mechanisms, engineering, and clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- The CD8 immgenT framework as a universal reference of mouse CD8αβ T cell differentiation states.bioRxiv : the preprint server for biology · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- The transcription factor ZEB2 mediates the antitumor efficacy of tumor-infiltrating lymphocytes in non-small cell lung cancer.Cell death & disease · 2025Article
- Overcoming immunotherapy resistance in non-small cell lung cancer: a narrative review of related factors.Immunotherapy · 2025Review
- Four-gene Prognostic Signature and Risk of Brain Metastasis of Lung Adenocarcinoma.Molecular carcinogenesis · 2025Article
- Cytokine Therapy in Bladder Cancer: Mechanisms, Efficacy, and Future Prospects.Current issues in molecular biology · 2025Review
- Lung Cancer-Intrinsic SOX2 Expression Mediates Resistance to Checkpoint Blockade Therapy by Inducing Treg-Dependent CD8+ T-cell Exclusion.Cancer immunology research · 2025Article
- Architects of immunity: How dendritic cells shape CD8Science immunology · 2025Review
- Cytokines in cancer.Cancer cell · 2025Review
- Review
- The Multifaceted Role of the IL-2 Cytokine Family in Melanoma: Mechanisms, Therapeutic Implications, and Immune Modulation.Journal of immunology research · 2025Review
- Current status of cytokine-induced killer cells and combination regimens in breast cancer.Frontiers in immunology · 2025Review
- Advancing non-small cell lung cancer treatment: the power of combination immunotherapies.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Engineered cytokine-based approaches for immunotherapy of cancer are poised to enter the clinic, with IL-12 being at the forefront. However, little is known about potential mechanisms of resistance to cytokine therapies. We found that orthotopic murine lung tumors were resistant to systemically delivered IL-12 fused to murine serum albumin (MSA, IL12-MSA) because of low IL-12 receptor (IL-12R) expression on tumor-reactive CD8+ T cells. IL2-MSA increased binding of IL12-MSA by tumor-reactive CD8+ T cells, and combined administration of IL12-MSA and IL2-MSA led to enhanced tumor-reactive CD8+ T cell effector differentiation, decreased numbers of tumor-infiltrating CD4+ regulatory T cells, and increased survival of lung tumor-bearing mice. Predictably, the combination of IL-2 and IL-12 at therapeutic doses led to significant dose-limiting toxicity. Administering IL-12 and IL-2 analogs with preferential binding to cells expressing Il12rb1 and CD25, respectively, led to a significant extension of survival in mice with lung tumors while abrogating dose-limiting toxicity. These findings suggest that IL-12 and IL-2 represent a rational approach to combination cytokine therapy whose dose-limiting toxicity can be overcome with engineered cytokine variants.
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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.