Wagner NB, Weide B, Gries M, et al. - Researchers investigated the efficacy of the tumor microenvironment-derived protein S100A8/A9 as a prognostic marker for melanoma patients, also in the setting of immunotherapy. Using a cDNA library and three independent tissue-microarrays (TMA), they analyzed S100A8/A9 gene and protein expression on melanocytic nevi, primary melanomas and metastases. Two independent cohorts of 354 stage III and stage IV melanoma patients as well as in two independent cohorts of patients treated with the PD-1 antibody pembrolizumab were examined for serum levels of S100A8/A9 using a specific ELISA. Relative to primary melanomas, melanoma metastases were noted to be correlated with an upregulation of S100A8 and S100A9 gene expression in cDNA analysis. Tissue samples of metastasizing primary melanomas vs non-metastasizing melanomas and melanomas of short-term survivors vs long-term survivors showed significantly higher numbers of infiltrating S100A8/A9 positive cells. Findings support the value of the tumor microenvironment-associated protein S100A8/A9 as a novel prognostic marker for metastasis and survival of metastatic melanoma patients. Further, it was identified as useful for predicting response to immunotherapy with pembrolizumab. Data thereby emphasize the importance of tumor microenvironment-derived factors as suitable biomarkers for melanoma.