We propose to characterize the response of neuroendocrine tumors to PD-1 inhibition in an ex vivo tissue slice culture model. Using this model, we will assess changes in RNA expression and changes in secretion of key immune mediators in response to treatment. In parallel, we will characterize key secreted immune markers and cytokines in the plasma of patients with advanced neuroendocrine tumors, and assess whether secretion patterns are associated with overall survival. Our findings should provide preliminary evidence of whether immune checkpoint inhibition has a biologic effect on neuroendocrine tumors, and more broadly should provide insights as to the potential role of secreted immune mediators in regulating neuroendocrine tumor growth.
da Silva A, Bowden M, Zhang S, Masugi Y, Thorner AR, Herbert ZT, Zhou CW, Brais L, Chan JA, Hodi FS, Rodig S, Ogino S, Kulke MH. Characterization of the Neuroendocrine Tumor Immune Microenvironment. Pancreas. 2018 Oct;47(9):1123-1129. doi: 10.1097/MPA.0000000000001150.