ArticleJournal for immunotherapy of cancer2023
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 16 citations in OpenAlex.
- CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells.iScience · 2026Article
- Elevated IgG levels induce an M2‑to‑M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas.Molecular medicine reports · 2026Article
- Article
- A proteogenomic atlas of 1032 brain metastases identifies molecular subtypes, immune landscapes, and therapeutic vulnerabilities.Nature communications · 2026Article
- Characterization of the tumor microenvironment in locally advanced gastric cancer and identification of spatially predictive biomarkers associated with beneficial neoadjuvant immunochemotherapy.Frontiers in immunology · 2026Article
- BCL-XbioRxiv : the preprint server for biology · 2025Article
- Beyond tumour suppression: cGAS-STING pathway in urologic malignancies: Context-dependent duality and therapeutic implications.Clinical and translational medicine · 2025Review
- BCL-xL dependency in chromophobe renal cell carcinoma.Cancer gene therapy · 2025Article
- Predictors of All-Cause In-Hospital Mortality in Patients With Malignant Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors.World journal of oncology · 2025Article
- Single-cell sequencing technology in renal cancer: insights into tumor biology and clinical application.Biomarker research · 2025Review
- Ambivalent roles of miRNAs in cancer development via modulating tumor-associated innate immune cells.BioImpacts : BI · 2025Review
- Gastric metastasis of renal cell carcinoma: features, mechanisms, and insights from existing literature.Frontiers in cell and developmental biology · 2025Review
- Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma.JCI insight · 2024Article
- TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.Cancer immunology, immunotherapy : CII · 2024Article
- Immunogenomics and spatial proteomic mapping highlight distinct neuro-immune architectures in melanoma vs. non-melanoma-derived brain metastasis.BJC reports · 2024Article
- Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.Journal for immunotherapy of cancer · 2024Article
- Multiplex protein imaging in tumour biology.Nature reviews. Cancer · 2024Review
- Multifaceted roles of cGAS-STING pathway in the lung cancer: from mechanisms to translation.PeerJ · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe tumor microenvironment (TME) contributes to cancer progression and treatment response to therapy, including in renal cell carcinoma (RCC). Prior profiling studies, including single-cell transcriptomics, often involve limited sample sizes and lack spatial orientation. The TME of RCC brain metastases, a major cause of morbidity, also remains largely uncharacterized.
methodsWe performed digital spatial profiling on the NanoString GeoMx platform using 52 validated immuno-oncology markers on RCC tissue microarrays representing progressive stages of RCC, including brain metastases. We profiled 76 primary tumors, 27 adjacent histologically normal kidney samples, and 86 metastases, including 24 brain metastases.
resultsWe observed lower immune checkpoint (TIM-3 and CTLA-4), cytolytic (GZMA and GZMB), and T cell activation (CD25) protein expression in metastases compared with primary tumors in two separate cohorts. We also identified changes in macrophages in metastases, with brain metastases-susceptible patients showing less M1-like, inflammatory macrophage markers (HLA-DR and CD127) in metastatic samples. A comparison of brain metastases to extracranial metastases revealed higher expression of the anti-apoptotic, BCL-2-family protein BCL-XL and lower expression of the innate immune activator STING in brain metastases. Lower TIM-3 and CD40 in the TME of brain metastases appear to be associated with longer survival, a finding that requires further validation.
conclusionsCompared with primary tumors, RCC metastases, including brain metastases, express lower levels of numerous markers of immune activation and current or investigational therapeutic targets. Our findings may have important implications for designing future biomarker and treatment studies and may aid in development of brain metastases-specific therapies.
Indexed as
Identifiers
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.