# Cytokine Profiling in Cutaneous Melanoma: The Emerging Role of Interleukins in Prognostic Stratification with an Up-to-Date Overview of Published Data

**Authors:** Paola Negovetić, Klara Gaćina, Nika Franceschi, Marija Buljan

PMC · DOI: 10.3390/jpm16020120 · 2026-02-15

## TL;DR

This paper reviews how interleukins, a type of cytokine, influence the progression and prognosis of cutaneous melanoma, offering insights into immune regulation and personalized treatment strategies.

## Contribution

The paper provides an up-to-date synthesis of interleukin roles in melanoma prognosis and immune response, highlighting their potential for personalized medicine.

## Key findings

- Elevated IL-2 levels correlate with sentinel lymph node positivity in early melanoma.
- Increased IL-6 and IL-8 are linked to advanced disease and reduced survival.
- IL-17 signatures predict response to immune checkpoint inhibition in BRAFV600-mutant melanoma.

## Abstract

Background: Cutaneous melanoma is an aggressive malignancy driven by complex interactions between tumor cells and the host immune system. Tumor progression is shaped not only by intrinsic tumor characteristics but also by immune-mediated processes within the tumor microenvironment. Cytokines, particularly interleukins, are key regulators of inflammation, immune cell recruitment, and tumor behavior. Cytokine profiling provides an integrated assessment of soluble immune mediators from tumor and stromal cells, reflecting both local and systemic immune responses. Methods: This narrative review summarizes and synthesizes the current literature addressing the biological and clinical relevance of selected interleukins, including IL-6, IL-8, IL-10, IL-2, IL-17, and IL-18, in cutaneous melanoma. Published data were evaluated with a focus on their immunomodulatory functions and potential implications for prognostic assessment. Results: Interleukins demonstrated distinct and context-dependent prognostic and predictive relevance in cutaneous melanoma. Elevated IL-2 levels correlated with sentinel lymph node positivity, supporting its prognostic value in early disease. Increased circulating IL-6 and IL-8 were consistently associated with tumor burden, advanced disease, and reduced survival. IL-10 expression reflected tumor progression and immune modulation. IL-17 signatures predicted response to combined immune checkpoint inhibition, particularly in BRAFV600-mutant melanoma. IL-18 exhibited dual roles, associating with both immune activation and favorable outcomes depending on tumor context. Conclusions: Interleukin profiling offers a biologically relevant framework for understanding immune regulation in cutaneous melanoma. Integrating interleukin signatures into prognostic models may support more refined risk stratification and advance the implementation of personalized medicine approaches in melanoma management.

## Linked entities

- **Proteins:** IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), IL10 (interleukin 10), IL2 (interleukin 2), IL17A (interleukin 17A), IL18 (interleukin 18)
- **Diseases:** cutaneous melanoma (MONDO:0005012)

## Full-text entities

- **Genes:** STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, IL17C (interleukin 17C) [NCBI Gene 27189] {aka CX2, IL-17C}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, CXCR2 (C-X-C motif chemokine receptor 2) [NCBI Gene 3579] {aka CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CXCR1 (C-X-C motif chemokine receptor 1) [NCBI Gene 3577] {aka C-C, C-C-CKR-1, CD128, CD181, CDw128a, CKR-1}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 22329] {aka CD106, Vcam-1}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, IL10RA (interleukin 10 receptor subunit alpha) [NCBI Gene 3587] {aka CD210, CD210a, CDW210A, HIL-10R, IL-10R1, IL10R}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, IL18R1 (interleukin 18 receptor 1) [NCBI Gene 8809] {aka CD218a, CDw218a, IL-18R, IL-18R-alpha, IL-18Ralpha, IL-1Rrp}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, Kitl (kit ligand) [NCBI Gene 17311] {aka Clo, Con, Gb, Kitlg, Mgf, SCF}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, IL18RAP (interleukin 18 receptor accessory protein) [NCBI Gene 8807] {aka ACPL, CD218b, CDw218b, IL-18R-beta, IL-18RAcP, IL-18Rbeta}, TP73 (tumor protein p73) [NCBI Gene 7161] {aka CILD47, P73}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL17F (interleukin 17F) [NCBI Gene 112744] {aka CANDF6, IL-17F, ML-1, ML1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}
- **Diseases:** Chronic inflammation (MESH:D007249), benign melanocytic and Spitz nevi (MESH:D009508), injury to (MESH:D014947), Melanoma (MESH:D008545), Tumor (MESH:D009369), metastatic (MESH:D000092182), nonmelanoma skin cancer (MESH:D012878), carcinogenesis (MESH:D063646), hypoxia (MESH:D000860), hepatic metastasis (MESH:D009362), immune dysfunction (MESH:D007154), stages III-IV disease (MESH:D007676), toxicities (MESH:D064420), advanced disease (MESH:D020178), lymph node metastases (MESH:D008207), Cutaneous Melanoma (MESH:C562393), basal cell carcinoma (MESH:D002280)
- **Chemicals:** tocilizumab (MESH:C502936), ipilimumab (MESH:D000074324), BRAFV600 (-), pembrolizumab (MESH:C582435), nivolumab (MESH:D000077594)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12942203