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

in ACS nano by Adrien Krug, Lena M Ernst, Rana Mhaidly, Joana Ramis, Muriel F Gusta, Neus G Bastus, Adriana Martinez-Turtos, Marie Tosolini, Léa Di Mascio, Gamze Tari, Laurent Boyer, Philippe Gaulard, François Lemonnier, Jean-Ehrland Ricci, Els Verhoeyen, Victor Puntes

TLDR

  • The study shows that ROS scavenging cerium oxide (CeO) nanoparticles can restore immune function and improve survival rates in high-energy-demanding angioimmunoblastic T-cell lymphoma (AITL).
  • The CeO nanoparticles selectively accumulate in the spleen, reducing CD4+ PD-1T cells driving malignancy and activating exhausted CD8+ T cells to restore antitumor function.
  • This strategy shows promise for treating AITL and other high-energy-demanding cancers.

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-1T cells show increased mitochondrial activity and Reactive oxygen species (ROS) accumulation. Here, we report that administration of ROS scavenging cerium oxide (CeO) nanoparticles in an AITL preclinical mouse model leads to their preferential accumulation in the spleen, where the CD4+ PD-1T 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.

Overview

  • The study investigates the relationship between cancer cell survival and proliferation with metabolic activity and oxidative stress in high-energy-demanding angioimmunoblastic T-cell lymphoma (AITL).
  • The researchers aimed to experimentally validate the correlation between increased energy demand, mitochondrial activity, PD-1 expression, ROS production, and immune suppression, as well as evaluate the efficacy of ROS scavenging cerium oxide (CeO) nanoparticles in treating AITL.
  • The study aimed to answer the question: whether ROS scavenging can restore immune function and improve survival rates in AITL, and whether this strategy is safe for healthy cells and tissues.

Comparative Analysis & Findings

  • Cerium oxide (CeO) nanoparticles were shown to preferentially accumulate in the spleen, where CD4+ PD-1T cells driving malignancy were significantly reduced.
  • The administration of CeO nanoparticles led to the activation of previously exhausted cytotoxic CD8+ T cells, restoring their potent antitumor function.
  • As a result, survival rates dramatically increased without observed toxicity to healthy cells or tissues.

Implications and Future Directions

  • The study highlights the potential therapeutic benefits of targeting ROS scavenging in treating high-energy-demanding cancers like AITL.
  • Future research directions could involve investigating the mechanism of action of ROS scavenging in AITL, as well as extending this approach to other high-energy-demanding cancers.
  • This study also opens up new avenues for exploring combinatorial therapies that combine ROS scavenging with immunotherapy strategies to improve treatment outcomes.
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