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Record W4416754171 · doi:10.1101/2025.11.24.690170

NLRP1 Shapes Immune and Inflammatory Signatures in Human Melanoma but Not in Mouse Models

2025· preprint· W4416754171 on OpenAlexaff
Vitor Pedro Targhetta, Raquel de Souza Vieira, Hedden Ranfley, Cristiane Naffah de Souza Breda, Niels Olsen Saraiva Câmara

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammasome and immune disorders
Canadian institutionsPrincess Margaret Cancer Centre
FundersFundação de Amparo à Pesquisa do Estado de São Paulo
KeywordsMelanomaPyroptosisImmune systemInflammasomeNLRP1AIM2Function (biology)ReceptorGene

Abstract

fetched live from OpenAlex

Abstract Inflammasomes are multiprotein complexes that activate pro-caspase-1, leading to the maturation of the pro-inflammatory cytokines IL-1β and IL-18. Nlrp1 , the first receptor identified with inflammasome-forming capacity, is highly expressed in both the skin and immune cells. Despite its prominent role in these tissues, the function of Nlrp1 in melanoma remains poorly characterized. In this study, we investigated the impact of Nlrp1 on melanoma patient survival and found that its expression is associated with improved prognosis and with a co-expression network enriched for pro-inflammatory genes. However, in murine models, neither Nlrp1 expression nor activation significantly affected melanoma development or progression. Similarly, pharmacological activation of Nlrp1 using Val-Boro-Pro (VbP) did not alter tumor growth or the local inflammatory profile in mice but directly influenced CD25 + cell generation and glucose uptake in in vitro models. Finally, we demonstrated that a melanoma risk score can be constructed based on genes specific to inflammasome and pyroptosis pathways. Collectively, our findings reveal species-specific differences in NLRP1 function between humans and mice and support the potential of inflammasome-related pathways as prognostic biomarkers and therapeutic targets in human cancers.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.210
Teacher spread0.202 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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