ArticleJournal of translational medicine2026
The complement system contributes to the immunosuppressive microenvironment of uveal melanoma.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUveal melanoma (UM) is a rare disease, but the most common intraocular malignancy in adults, with incidence rates in Europe ranging from 1.3 to 8.6 cases per million annually. Although local tumor control is often effective, up to 50% of patients develop systemic metastases for which treatment options remain limited. Complement gene expression has been linked to poor prognosis in UM, but its role in tumor biology is still not well understood.
methodsHypothesizing that dysregulated complement signaling fosters an immunosuppressive tumor microenvironment and promotes progression, this study for the first time investigated the role of the complement system in primary and metastatic UM. We applied an integrated approach utilizing publicly available UM bulk, single-cell RNA sequencing and proteomic data as well as immunohistochemistry of human samples, and RNA expression analysis. We also compared complement associated protein expression between primary UM (pUM) and normal ocular tissue, as well as metastatic UM (mUM) and normal liver.
resultspUM preferentially expressed early complement components over terminal elements, with early factors demonstrating prognostic significance. High-risk tumors showed elevated secretion of C1S and C1R proteases. Fibroblasts and macrophages constituted the main sources of complement genes. mUM exhibited an expanded role for C3 relative to primary tumors. Fibroblasts were predicted to drive formation of an immunosuppressive microenvironment via RPS19–C5AR1, C3–ITGAM, and C3–C3AR interactions with macrophages and myeloid-derived suppressor cells. Trajectory analysis identified the iCAF phenotype as a transitional state between normal liver fibroblasts and mCAF, suggesting fibroblast education and involvement in pre-metastatic niche formation.
conclusionOur findings identified C1S and C3 complement components as promising therapeutic targets. The availability of clinically approved complement inhibitors supports potential repurposing for high-risk pUM and mUM, offering a novel strategy to improve treatment outcomes.
Indexed as
Identifiers
What Socratic 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 Socratic graph.