Precision Immuno-Oncology Across Organ Systems: Cytokine–lncRNA Networks Linking Chronic Inflammation, Neurodegeneration, and Cancer

Psoriasis, atopic dermatitis (AtD), and Alzheimer’s disease (AD) are chronic inflammatory disorders traditionally examined within isolated organ systems, but are increasingly recognized as manifestations of a shared immunometabolic architecture with direct relevance to cancer biology. Synthesizing multi-omics with transcriptomic and clinical evidence, this review delineated the conserved cytokine-driven networks linking cutaneous, neural, and oncologic inflammation. Core inflammatory loops centered on interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, IL-17A/F, and IL-23 were found to converge on Janus kinase (JAK)–signal transducer and activator of transcription (STAT), nuclear factor κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling across keratinocytes-, microglia-, and tumor-associated immune cells. Transcription factors (peroxisome proliferator activated receptor γ (PPARG), zinc finger protein, FOG family member 2 (ZFPM2), zinc finger protein 415 (ZNF415), H2.0 like homeobox (HLX), and anomalous homeobox (ANHX)) and long non-coding RNAs (metastasis associated lung adenocarcinoma transcript 1 ( MALAT1 ), nuclear enriched abundant transcript 1 ( NEAT1 ), psoriasis susceptibility-related induced by stress ( PRINS ), and β-site APP cleaving enzyme 1 antisense transcript ( BACE1-AS )) were found to form feed-forward regulatory circuits that sustained immune activation across tissues. Comparative immunogenomic analyses revealed overlapping inflammatory states among lesional skin, the Alzheimer’s brain, and tumor microenvironments, supporting a unified inflammatory continuum. Biologic agents and JAK inhibitors, originally developed for dermatologic diseases, were observed to provide mechanistic and therapeutic entry points for modulating neuroinflammation and tumor-promoting immune niches. These findings demonstrate that integrative systems biology and artificial intelligence (AI)-driven multimodal modeling frameworks enable immune-state stratification beyond organ boundaries, offering a precision-guided paradigm for cross-disease immunomodulation in neurodegeneration and cancer.