Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles

Proton pump inhibitors have been explored for potentiating cancer therapies via reverting the tumor acidity and promoting the activation of anti-tumor immune responses. To regulate the intracellular pH of melanoma and immunosuppressive myeloid cells, we developed poly(L-lactide-co-glycolide) nanoparticles loaded with esomeprazole (ESO-NPs). The effect of ESO-NPs on melanoma cells was observed as alkalinization and reduction of melanin content accompanied by a decrease of microphthalmia-associated transcription factor (MITF), poliovirus receptor (PVR), and programmed death ligand 1 (PD-L1) immune checkpoint expression. ESO-NP treatment of melanoma-patient-derived and in vitro-induced myeloid-derived suppressor cells (MDSCs) reduced the expression of immunosuppression-associated molecules PD-L1, CD206, and CD163 on patient-derived myeloid cells while inducing the expression of co-stimulatory molecule CD86 and HLA-DR in the in vitro model. Our findings suggest that reprogramming the intracellular pH of melanoma and immune-suppression-associated myeloid cells with ESO-NPs can modulate the expression of proteins involved in resistance to cancer therapy and immunosuppression, thus potentially improving the response to immunotherapies.

Keywords

Biological sciences, Biotechnology, Immunology, Medical biotechnology

Subject (DDC)

610 - Medizin und Gesundheit

Project

Event

Exhibition start date

Exhibition end date

Conference start date

Conference end date

Date of the last check

ISBN

ISSN

2589-0042

Language

English

Created during FHNW affiliation

Yes

Strategic action fields FHNW

Future Health

Publication status

Published

Review

Peer review of the complete publication

Open access category

Gold

License

Citation

Cerioli, N., Bououdina, W., Mereu, A., Natsaridis, E., Salsetta, J., Cova, A., Lupoli, G., D’Angelo, E., Rivoltini, L., Figdor, C. G., Huber, V., & Tagit, O. (2025). Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles. iScience, 28(1), 111559. https://doi.org/10.1016/j.isci.2024.111559

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