Scavenging Reactive Oxygen Species by Cerium Oxide Nanoparticles Prevents Death in a Peripheral T Cell Lymphoma Preclinical Mouse Model

Cancer cell survival and proliferation are correlated with increased metabolic activity and consequent oxidative stress, driving metabolic shifts that interfere with the immune response to malignant cells. This is the case of high-energy-demanding angioimmunoblastic T cell lymphoma (AITL), a highly aggressive cancer with poor survival rates, where malignant CD4+ PD-1<sup>high</sup> T cells show increased mitochondrial activity and Reactive oxygen species (ROS) accumulation. Here, we report that administration of ROS scavenging cerium oxide (CeO<sub>2</sub>) nanoparticles in an AITL preclinical mouse model leads to their preferential accumulation in the spleen, where the CD4+ PD-1<sup>high</sup> T cells driving malignancy were significantly reduced. This was accompanied by activation of previously exhausted cytotoxic CD8+ T cells, restoring their potent antitumor function. As a result, survival rates dramatically increase with no observed toxicity to healthy cells or tissues. Overall, it highlights the correlation between increased energy demand, increased mitochondrial mass, increased PD-1 expression, increased ROS production, and immune suppression and how this vicious loop can be stopped by scavenging ROS.

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Publication Details

Journal
ACS Nano
Published
2025-05-09
DOI
https://doi.org/10.1021/acsnano.5c02860
Citations
3
Primary Topic
Advanced Nanomaterials in Catalysis
Type
article
Field-Weighted Citation Impact
1.55
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article

Scavenging Reactive Oxygen Species by Cerium Oxide Nanoparticles Prevents Death in a Peripheral T Cell Lymphoma Preclinical Mouse Model

Els Verhoeyen, Rana Mhaidly, Philippe Gaulard, François Lemonnier et al.
3 citations
ACS Nano
Advanced Nanomaterials in Catalysis
1.55
article

Scavenging Reactive Oxygen Species by Cerium Oxide Nanoparticles Prevents Death in a Peripheral T Cell Lymphoma Preclinical Mouse Model

Els Verhoeyen, Rana Mhaidly, Philippe Gaulard, François Lemonnier, Jean‐Ehrland Ricci, Neus G. Bastús, Víctor Puntes, Marie Tosolini, Adriana Martinez-Turtos, Adrien Krug, Joana Ramis, Muriel F. Gustà, Laurent Boyer, Lena M. Ernst, Gamze Tari, Léa Di Mascio
article en
3 citations

Abstract

Cancer cell survival and proliferation are correlated with increased metabolic activity and consequent oxidative stress, driving metabolic shifts that interfere with the immune response to malignant cells. This is the case of high-energy-demanding angioimmunoblastic T cell lymphoma (AITL), a highly aggressive cancer with poor survival rates, where malignant CD4+ PD-1<sup>high</sup> T cells show increased mitochondrial activity and Reactive oxygen species (ROS) accumulation. Here, we report that administration of ROS scavenging cerium oxide (CeO<sub>2</sub>) nanoparticles in an AITL preclinical mouse model leads to their preferential accumulation in the spleen, where the CD4+ PD-1<sup>high</sup> T cells driving malignancy were significantly reduced. This was accompanied by activation of previously exhausted cytotoxic CD8+ T cells, restoring their potent antitumor function. As a result, survival rates dramatically increase with no observed toxicity to healthy cells or tissues. Overall, it highlights the correlation between increased energy demand, increased mitochondrial mass, increased PD-1 expression, increased ROS production, and immune suppression and how this vicious loop can be stopped by scavenging ROS.

ACS NanoVol. 19(19)
Université Claude Bernard Lyon 1 (FR), École Normale Supérieure de Lyon (FR), Institució Catalana de Recerca i Estudis Avançats (ES), Centre National de la Recherche Scientifique (FR), Université Toulouse III - Paul Sabatier (FR), Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Université Paris-Est Créteil (FR), Université Côte d'Azur (FR), Instituto de Salud Carlos III (ES), Centre de Recherches en Cancérologie de Toulouse (FR), Institut Català de Nanociència i Nanotecnologia (ES), La Ligue Contre le Cancer (FR), Vall d'Hebron Institut de Recerca (ES), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES), Observatoire de la Côte d’Azur (FR), Hôpitaux Universitaires Henri-Mondor (FR), Hôpital Albert-Chenevier (FR), Institut Mondor de Recherche Biomédicale (FR)
Openalex Percentile: Top 18%
Advanced Nanomaterials in Catalysis
1.55
DOIOpen Access PDFOpenAlex
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