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Write a short summary of the research’s main findings and how this work has moved the field forward.

This preprint analyzes transcriptomic data from systemic lupus erythematosus (SLE) and melanoma patients to uncover shared immune and epigenetic pathways. Key findings include an "immune signature" (147 genes, enriched in interferon signaling and epigenetic regulators like ASF1B and EZH2) upregulated in SLE and melanoma responders to immune checkpoint blockade (ICB), and a "cell cycle signature" (157 genes, dominated by CDK1 and CCNB1) linked to ICB resistance in melanoma non-responders, with partial overlap in SLE. Validation in independent datasets confirmed the immune signature's relevance (AUC=0.780 in SLE) and the cell cycle signature's specificity to melanoma. In TCGA-SKCM, the cell cycle signature strongly predicted worse survival (OS HR=15.634, p=0.011; PFS HR=8.484, p=0.019), while a composite score improved prognostic utility (OS HR=0.141, p=0.004). Connectivity Map analysis proposed repurposed drugs like mTOR inhibitors, proteasome inhibitors, HDAC inhibitors, and statins. This work advances the field by revealing molecular convergence between autoimmunity and cancer immunotherapy, offering novel biomarkers for ICB response and survival in melanoma, and suggesting therapeutic repurposing opportunities to target shared pathways, potentially bridging SLE and oncology research.

Major issues

• List significant concerns about the research, if there are any.

• The research relied on transcriptomic data without functional or experimental validation, limiting causal inferences about the identified signatures and proposed mechanisms.

• Also the sample sizes is small in primary datasets (e.g., GSE211700: n=30 for SLE; GSE168204: unclear after filtering), which may reduce statistical power and generalizability.

• They also used bulk RNA-seq, which lacks cell-type resolution and could confound immune vs. tumor signals in melanoma.

• Moderate biomarker performance (AUCs 0.6567–0.780), suggesting limited clinical utility without further refinement.

Minor issues

• List concerns that would improve the overall flow or clarity but are not critical to the understanding and conclusions of the research.

• Numerous typos and grammatical errors (e.g., "pipline" for "pipeline", "differential expressied" for "differentially expressed", "pervious" for "previous"), which affect readability.

• Inconsistent referencing and incomplete supplements (e.g., full DEG lists referenced to a prior preprint but not included here).

• Limited discussion of confounders (e.g., age, sex, treatments) in survival analyses.

• The abstract and methods sections were overly dense , which could benefit from clearer subheadings or flow diagrams for better accessibility.

Competing interests

The authors declare that they have no competing interests.