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. 2025 Jul 12:e05729.
doi: 10.1002/advs.202505729. Online ahead of print.

Nanomaterials Trigger Functional Anti-Tumoral Responses in Primary Human Immune Cells

Vincent Mittelheisser  1   2   3   4   5   6 , Olivier Lefebvre  1   2   3   4   5 , Mainak Banerjee  5   6   7 , Shayamita Ghosh  5   6   7 , Amandine Dupas  1   2   3   4   5 , Marie-Charlotte Diringer  5   6   7 , Juliette Blumberger  5   6   7 , Louis Bochler  1   2   3   4   5 , Sébastien Harlepp  5   6   7 , Annabel Larnicol  1   2   3   4   5 , Angélique Pichot  2   3   4   8 , Tristan Stemmelen  2   3   4   8 , Anne Molitor  2   3   4   9 , Chloé Moritz  9 , Christine Carapito  9 , Raphaël Carapito  2   3   4   8   10 , Loïc J Charbonnière  11 , François Lux  12   13 , Olivier Tillement  12 , Jacky G Goetz  1   2   3   4   5 , Alexandre Detappe  5   6   7   11
Affiliations

Nanomaterials Trigger Functional Anti-Tumoral Responses in Primary Human Immune Cells

Vincent Mittelheisser et al. Adv Sci (Weinh). .

Abstract

Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications are characterized. After a pre-screen to evaluate the toxicity of these nanomaterials on immune cells, ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs are selected for further investigation. Bulk RNA-sequencing and flow cytometry analysis showcase that PLGA NPs trigger a transcriptional priming toward activation in NK and pan T cells. While PLGA NPs improved NK cells anti-tumoral functions in a cytokines-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation. Altogether, PLGA NPs are identified as an attractive strategy for reactivating the immune system of cancer patients.

Keywords: immunotherapy; nanomaterial; proteogenomics.

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