ArticleJCI insight2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Cell-based cancer immunotherapy: milestones, mechanistic insights, and emerging therapeutic directions.Acta pharmacologica Sinica · 2026Review
- CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells.iScience · 2026Article
- Anti-PD1-IL18 immunoconjugate promotes effector T cell-mediated antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- The seventh kidney cancer research summit: progress in accelerating cures.The oncologist · 2026Article
- Advances in Cancer Immunotherapy for Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- IL-18 suppresses retinoblastoma growth while concomitantly inducing an inflammation-/stress-associated and immune-remodeling response.Cancer cell international · 2026Article
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- IL-18-Mediated Tumor Immune Evasion.Current issues in molecular biology · 2026Review
- Single-cell differential abundance detection: A new angle on dissecting tumor heterogeneity.World journal of clinical oncology · 2026Review
- Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.Frontiers in immunology · 2026Review
- A Review of Immunotherapy in Renal Cell Carcinoma: Current Landscape and Future Directions.Cancers · 2025Review
- Immunotherapy for Renal Cell Carcinoma-What More is to Come?Targeted oncology · 2025Review
- Overcoming resistance to PD-1 and CTLA-4 blockade mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
- Characteristics of the tumor microenvironment and potential immunotherapy strategies in renal cell carcinoma.Frontiers in immunology · 2025Review
- The dual roles of human PYHIN family proteins in cancer: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
The cytokine IL-18 has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18's anticancer efficacy. A decoy-resistant form of IL-18 (DR-18) that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential has recently been developed. Here, we investigated the therapeutic potential of DR-18 in renal cell carcinoma (RCC). Using pantumor transcriptomic data, we found that clear cell RCC had among the highest expression of IL-18 receptor subunits and IL18BP of tumor types in the database. In samples from patients with RCC treated with immune checkpoint inhibitors, IL-18BP protein expression increased in the tumor microenvironment and in circulation within plasma in nonresponding patients, and it decreased in the majority of responding patients. We used immunocompetent RCC murine models to assess the efficacy of DR-18 in combination with single- and dual-agent anti-PD-1 and anti-CTLA-4. In contrast to preclinical models of other tumor types, in RCC models, DR-18 enhanced the activity of anti-CTLA-4 but not anti-PD-1 treatment. This activity correlated with intratumoral enrichment and clonal expansion of effector CD8+ T cells, decreased Treg levels, and enrichment of proinflammatory antitumor myeloid cell populations. Our findings support further clinical investigation of the combination of DR-18 and anti-CTLA-4 in RCC.
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