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

GSE342540 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2026/08/07 Platform GPL24676
Summary
Dendritic cells (DCs) are crucial for eliciting cytotoxic CD8+ T cell responses against intracellular pathogens, viruses and cancer. DC-based vaccines can stimulate both cytotoxic and humoral immunity, as well as memory against cancer. However, efficacy has remained low, leaving room for improvement. Our previous work using conditional Stim1 knock-out mice highlighted the importance of store-operated calcium entry (SOCE) in promoting DC migration, phagosome maturation and DC_x0002_driven CD8+ T cell responses. Yet its potential as a target to improve DC-mediated immune stimulation remains incompletely understood. We hypothesized that transient pharmacological modulation of SOCE signaling could boost DC-mediated T cell activity. 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.
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Direct links to NCBI, no account and no request form: the whole study as GSE342540_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1508171 and SRA study SRP724479. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × MoDCs, CTR, biol vs 3 × MoDCs, pBr, biol vs 3 × MoDCs, Tg, biol

Supports a between-group comparison across 9 samples.

3 replicated groups read from 9 sample titles; they account for 9 of them. Check it against the sample list below before relying on it.

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