Immunotherapy with PD-1 antibodies has greatly increased prognosis of patients with advanced melanoma.,Identifying biomarkers that predict overall survival (OS) and response to immunotherapy is important.,OS and best overall response according to RECIST version 1.1 were analysed, and S100B and lactate dehydrogenase (LDH) serum levels were assessed retrospectively in 152 patients treated with anti-PD-1, and in 86 patients treated with anti-PD-1 plus anti-CTLA-4 antibodies at University Hospital Tuebingen, Germany.,In the pembrolizumab group, patients with elevated baseline S100B or LDH exhibited significantly impaired OS compared with patients with normal S100B (1-year OS: 51.1% vs 83.1%, log-rank P < .0001) and normal LDH (1-year OS: 44.4% vs 80.8%, P = .00022), respectively.,LDH increases of >25% and S100B increases of >145% compared to baseline were significantly associated with impaired OS (both P < .0001).,In patients treated with ipilimumab and nivolumab, baseline S100B and increasing S100B levels of >145% as well as baseline LDH were associated with impaired OS (P < .0001, P = .00060, and P = .0050, respectively), whereas increasing LDH of >25% was not (P = .64).,S100B could serve as a strong baseline marker for OS in melanoma patients receiving anti-PD-1 therapy.,Rising S100B levels during the first weeks of therapy could help guide treatment decisions.
Significant tumor regressions have been observed in up to 70% of patients receiving adoptively transferred autologous melanoma-reactive tumor infiltrating lymphocytes (TIL) 1,2, and in pilot trials, 40% of treated patients experienced complete regressions of all measurable lesions for at least five years following treatment 3.,To evaluate the potential association between the ability of TIL to mediate durable regressions and their ability to recognize potent antigens that presumably include mutated gene products, a novel screening approach was developed that involved mining whole exome sequence data to identify the mutated proteins that were expressed in patient tumors.,Candidate mutated T cell epitopes that were identified using an MHC binding algorithm 4 were then synthesized and evaluated for recognition by TIL.,Using this approach, mutated antigens expressed on autologous tumor cells were identified as targets of three TIL that were associated with objective tumor regressions following adoptive transfer.,This simplified approach, which avoids the need to generate and laboriously screen cDNA libraries from tumors, may represent a generally applicable method for identifying mutated T cell antigens expressed in melanoma as well as other tumor types.