Store-operated calcium signaling modulators improve a dendritic cell-based vaccine against melanoma

Here, a targeted screen of SOCE modulators identified two compounds, thapsigargin (Tg) and para-bromo-2-aminoethyl diphenylborinate (pBr), that improved T cell proliferation, IL-2, and IFNG secretion in mouse and human DC:T cell co-cultures. In a B16 melanoma model, DC vaccines boosted with either compound reduced tumor growth by 50% and doubled the median survival benefit, increasing infiltration of activated CD8+ T cells, CD4+ T, natural killer, CD80+ B cells, and M1 macrophages.

Neither compound affected the surface expression of MHC-I-peptide complexes, MHC-II, CD86, nor DC migration, although thapsigargin promoted antigen retention. Bulk RNA sequencing revealed instead broad changes in pathways regulating secretion, where cytokine array analysis confirmed both compounds boosted secretion of several immunomodulatory factors. Together, this work identifies SOCE as a druggable axis that may be exploited to boost DC-mediated T cell activation and improve DC-based anticancer therapies.