Skin-Test Infiltrating Lymphocytes Predict Clinical Outcome of Dendritic Cell Based Vaccination in Metastatic Melanoma

ABSTRACT Introduction The identification of responding patients early during treatment would greatly improve the efficacy of novel and costly immunotherapies. Bioassays which accurately link preceding immune responses to clinical outcome are therefore needed. The mainstay of immunotherapy is to induce, enhance or sustain TAA-specific effector T cell immunity. Consequently, evaluation of the migratory-, antigen recognition-, as well as the effector function of tumor-specific cellular responses is critical. Methods A large cohort of metastatic melanoma patients (n = 91) enrolled in dendritic cell (DC)-based vaccination protocols was retrospectively analyzed for overall survival (OS) in relation to skin-test infiltrating lymphocyte (SKIL) cultures characteristics. Increasingly stringent criteria were defined identify long-term survivors. Results The presence of TAA-specific CD8+ T cells (criterion I: detection by tetrameric MHC-peptide complexes) in SKIL cultures associated with improved OS; 14.1 versus 10.9 months, p = 0.055. Further analyses showed that the presence of multiple specificities was highly predictive for long-term survival. Tumor recognition by TAA-specific CD8+ T cells on peptide level (detected by specific production of Thelper 1 (Th1) cytokines (criterion II; e.g. IFNg and/or IL-2) or cytotoxicity and no Thelper 2 (Th2) cytokines) was strongly associated with improved OS; 14.2 versus 10.2 months, p = 0.003. Recognition of naturally processed antigen by specific production of Th1 cytokines or cytotoxicity and no Th2 cytokines ((criterion III), maximized the accuracy of the test; 24.1 versus 9.9 months, p = 0.001. Conclusion Our results demonstrate that analyzing SKIL cultures is a solid bioassay to predict overall survival in metastatic melanoma patients. This bioassay is simple, feasible and integrates multiple aspects of cellular functions needed for effective immune responses. Disclosure All authors have declared no conflicts of interest.