The CIt protocol: A blueprint to potentiate the immunogenicity of immunoproteasome-reprogrammed mesenchymal stromal cells.

ABSTRACT: Immunoproteasome-reprogrammed mesenchymal stromal cells (IRMs) can surpass dendritic cells at eliciting tumor-specific immunity. However, the current IRM vaccination regimen remains clinically unsuitable due to the relatively high dose of IRMs needed. Since the administration of a lower IRM dose triggers a feeble anti-tumoral response, we aimed to combine this vaccination regimen with different modalities to fine-tune the potency of the vaccine. In a nutshell, we found that the co-administration of IRMs and interleukin-12 accentuates the anti-tumoral response, whereas the cross-presentation potency of IRMs is enhanced via intracellular succinate build-up, delayed endosomal maturation, and increased endosome-to-cytosol plasticity. Stimulating phagocyte-mediated cancer efferocytosis by block

SUBMITTER: Bikorimana JP 

PROVIDER: S-EPMC9682353 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature