ArticleJournal of translational medicine2024
Single-cell and spatial transcriptomics reveal SPP1-CD44 signaling drives primary resistance to immune checkpoint inhibitors in RCC.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Global trends and hotspots of macrophage-related research in intervertebral disc degeneration from 2005 to 2025: a bibliometric and visualized analysis.Frontiers in immunology · 2026Pooled it
- A systematic review of the latest progress of drug resistance and clinical application of immunotherapy in renal cell carcinoma in the past five years based on bibliometrics.Human vaccines & immunotherapeutics · 2025Pooled it
- Integrating clinical trial landscapes and bibliometric analysis: unveiling the impact of PD-1/PD-L1 inhibitors on renal cell carcinoma research and therapeutic trajectories summary.Frontiers in immunology · 2025Pooled it
- Characterization of SPP1 + macrophages and their correlation with resistance to neoadjuvant chemotherapy in colorectal cancer liver metastasis.Molecular biomedicine · 2026Article
- Heterogeneous SPP1-expressing esophageal cancer cells license immunotherapy resistance by organizing an immunosuppressive niche.Neoplasia (New York, N.Y.) · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Article
- Uterine natural killer cell-mediated immune imbalance impairs uterine vascular remodeling and contributes to adverse pregnancy outcomes in dengue virus-infected mice.Microbiology spectrum · 2026Article
- Targeted suppression of SPP1 inhibits tumor invasion and metastasis in NRF2 hyperactivated cisplatin resistant HNSCC.Journal of translational medicine · 2026Article
- Identification of ribosomal stress related signature genes and immune microenvironment analysis in ovarian cancer based on multi-machine learning.Discover oncology · 2026Article
- SPP1Cell death & disease · 2026Article
- Global scientific growth and thematic development of spatial transcriptomics in oncology research.Discover oncology · 2026Article
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- CDKN1A/p21 Influences the Survival and Expansion of Breast Cancer Stem Cells after Oxidative Damage.Oncology research · 2026Article
- Combined Dihydroartemisinin and Eupatilin Suppress Prostate Cancer through AR-Associated Ferroptosis and Modulation of Macrophage-Tumor Crosstalk.Research (Washington, D.C.) · 2026Article
- Single-Cell Dissection of the Immune Microenvironment in Intrahepatic Metastasis of Multifocal Hepatocellular Carcinoma.Research (Washington, D.C.) · 2026Article
- Single-cell transcriptomics identifies SOCS3+ exhausted T cells as a biomarker facilitating clear cell renal cell carcinoma progression.Clinical and experimental medicine · 2025Article
- The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment.Cancer research · 2025Review
- Identification of immunosuppressive CD4Discover oncology · 2025Article
- Single-cell transcriptomic analysis reveals metastatic and immunosuppressive characteristics in meningioma brain-tumor interface.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundImmune checkpoint inhibitors (ICIs) are a cornerstone therapy for advanced renal cell carcinoma (RCC). However, significant rates of primary resistance hinder their efficacy, and the underlying mechanisms remain poorly understood. This study aims to unravel the tumor-immune interactions and signaling pathways driving primary resistance to ICIs in RCC.
methodsWe integrated single-cell RNA sequencing, spatial transcriptomics, and clinical sample analysis to investigate the tumor microenvironment and intercellular signaling. Advanced computational methods, including cell-cell communication networks, pseudotime trajectories, and gene set enrichment analysis (GSEA), were employed to uncover the underlying resistance mechanisms.
resultsCompared to the sensitive group, the primary resistance group exhibited a significant increase in SPP1-CD44 signaling-mediated interactions between tumor cells and immune cells. These interactions disrupted antigen presentation in immune effector cells and suppressed key chemokine and cytokine pathways, thereby impairing effective immune responses. In contrast, the sensitive group showed more active antigen presentation and cytokine signaling, which facilitated stronger immune responses. Furthermore, the interaction between SPP1-secreting tumor cells and CD44-expressing exhausted CD8 + T cells activated the MAPK signaling pathway within CD8 + Tex cells, exacerbating T cell exhaustion and driving the development of ICI resistance in RCC.
conclusionOur findings reveal a potential mechanism by which SPP1-CD44 signaling mediates tumor-immune cell interactions leading to ICI resistance, providing a theoretical basis for targeting and disrupting this signaling to overcome primary resistance in RCC.
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