Verena Paulitschke*
Department of Dermatology, Medical University Vienna
verena.paulitschke [at] meduniwien.ac.at
Abstract
Reliable biomarkers to predict or monitor response to anti-PD-1 therapy in metastatic melanoma remain unavailable. Noninvasive analysis of fingertip sweat has recently been proposed as a promising method to detect inflammatory signatures and tumor-related metabolic changes.
Finger sweat is collected at baseline, 3 weeks, and 3 months after initiation of therapy, alongside clinical data. In a preliminary study, patients treated with 480 mg nivolumab provided samples immediately before and after therapy. Sweat was analyzed by liquid chromatography–mass spectrometry (Orbitrap Exploris 480), followed by bioinformatic and statistical processing.
In prior work, we identified a serum signature of 10 proteins (CRP, LYVE1, SAA2, C1RL, CFHR3, LBP, LDHB, S100A8, S100A9, SAA1) associated with poor response to anti-PD-1 therapy. Extending this concept, we now apply fingertip sweat metabolomics as a noninvasive biomarker strategy. Preliminary analyses revealed elevated kynurenine (tryptophan metabolism), p-cresol sulfate (microbial dysbiosis), and markers of mitochondrial stress in melanoma patients’ sweat samples. These metabolites may serve as pharmacodynamic indicators during immunotherapy. A larger cohort is currently being evaluated at the predefined time points to validate these findings and explore additional metabolites. Plasma proteomics within our longitudinal cohort revealed a distinct regulation of immune-related proteins between responders and non-responders after three months of therapy. Responders were characterized by a significant upregulation of immunoglobulins and the Golgi-associated protein GLIPR2. Conversely, non-responders exhibited elevated levels of SPINK1, a marker closely associated with epithelial-mesenchymal transition (EMT) and therapeutic resistance. Protein set enrichment analysis (PSEA) further confirmed a selective enrichment of immunological functions exclusively in responders, indicating effective systemic immune activation. Integrating these proteomic findings with fingertip sweat and plasma metabolomics will provide a comprehensive, multi-omic perspective on treatment efficacy.
This study seeks to establish fingertip sweat profiling as an innovative, noninvasive platform for biomarker discovery in melanoma immunotherapy. Capturing metabolic processes at the patient level may enable early identification of non-responders, improve risk stratification, and provide mechanistic insights into resistance, all without imposing significant procedural burden.
Keywords: melanoma, immune therapy, biomarker