ArticleThe Journal of clinical investigation2024
VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 16 citations in OpenAlex.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Integrated WGCNA, Network Pharmacology, and UPLC-MS/MS Profiling for Investigating the Antitumor Effects of the Kansui Radix Dichloromethane Fraction Against Renal Cell Carcinoma with Experimental Validation.International journal of molecular sciences · 2026Article
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Hybrid Drug Delivery System Designed from Spatiotemporal Hierarchical Controlled-Release Strategy Co-Delivering Rutin and Resveratrol for Coordinated Anti-Tumor Immunotherapy.Pharmaceutics · 2026Article
- Single-cell and spatial multi-omics reveal mechanistic insights of FOLH1+ endothelial cells in clear cell renal cell carcinoma.Journal of translational medicine · 2026Article
- MT1G promotes the progression of ccRCC by suppressing ferroptosis through activation of the PI3K-AKT pathway.Translational oncology · 2026Article
- Natural Products in Clear Cell Renal Cell Carcinoma: Rewiring the VHL-HIF Axis, Metabolic Plasticity, and Tumor-Immune Interactions.International journal of molecular sciences · 2026Review
- Essential genetic mutations impair DNA damage repair and modulate tumor immune microenvironment in ccRCC.MedScience · 2026Review
- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
- Disulfidptosis induced by intermittent fasting and metformin enhances the efficacy of anti-PD-1 therapy in renal cancer.Cell communication and signaling : CCS · 2026Article
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- Obesity-driven metabolic reprogramming and immune dysfunction in renal cancer.Frontiers in immunology · 2026Review
- The emerging role of oncolytic virotherapy in genitourinary malignancies.Frontiers in cell and developmental biology · 2026Review
- Divergent cytotoxic and inflammatory functions of intratumoral Vδ2Frontiers in immunology · 2026Article
- Immune Landscape and Application of Immune Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2025Review
- A pan-cancer analysis revealedPrecision clinical medicine · 2025Article
- Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.International journal of molecular sciences · 2025Review
- Osalmid sensitizes clear cell renal cell carcinoma to navitoclax through a STAT3/BCL-XL pathway.Cancer letters · 2025Article
- Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma.Journal of biomedical science · 2025Review
- Spatially segregated APOETheranostics · 2025Article
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23 authors at 6 institutions in 1 country.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC pathogenesis and promotes stabilization of HIF. Whether VHL loss in cancer cells affects immune cells in the TME remains unclear. Using Vhl WT and Vhl-KO in vivo murine kidney cancer Renca models, we found that Vhl-KO tumors were more infiltrated by immune cells. Tumor-associated macrophages (TAMs) from Vhl-deficient tumors demonstrated enhanced in vivo glucose consumption, phagocytosis, and inflammatory transcriptional signatures, whereas lymphocytes from Vhl-KO tumors showed reduced activation and a lower response to anti-programmed cell death 1 (anti-PD-1) therapy in vivo. The chemokine CX3CL1 was highly expressed in human ccRCC tumors and was associated with Vhl deficiency. Deletion of Cx3cl1 in cancer cells decreased myeloid cell infiltration associated with Vhl loss to provide a mechanism by which Vhl loss may have contributed to the altered immune landscape. Here, we identify cancer cell-specific genetic features that drove environmental reprogramming and shaped the tumor immune landscape, with therapeutic implications for the treatment of ccRCC.
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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.