Dr. Florence Gazeau - Nanomedicine approaches to modulate the tumor microenvironment

Dr. Florence Gazeau

MSC Med, CNRS / Université Paris Cité

Nanomedicine approaches to modulate the tumor microenvironment
I will present different approaches using inorganic nanoparticles or stem cell-derived extracellular vesicles activable by an external field to target and modulate the tumor microenvironment by thermal phototherapy or photodynamic therapy in models of desmoplastic tumors and peritoneal metastasis. The rigidity and mechanical heterogeneity of solid tumors being an important factor in their progression and resistance to treatment, we will show how acting on the extracellular matrix and softening the tumor can improve the migration of T cells in different preclinical models and promote the response to immunotherapies. Measurement of tumor stiffness by elastography could be a physical biomarker, accessible by imaging, to stratify patients who may benefit from antistromal therapy to increase their response to immunotherapy. Moreover metallic nanoparticles and extracellular vesicles can exert immunomodulatory effects on their own on the tumor microenvironment that can be enhanced or reversed by photo-activation in solid tumors. Nanomedicine strategies, exploiting the interplay between the nanoparticles, the different components of tumor microenvironment and their physical activation by external field at the most favorable therapeutic window could be valuable for future cancer treatment associated to immunotherapeutic approaches.

Selected references

Immune Reprogramming Precision Photodynamic Therapy of Peritoneal Metastasis by Scalable Stem Cell Derived Extracellular Vesicles. A Pinto, I Marangon, J Méreaux, A Nicolás-Boluda, G Lavieu, C Wilhelm, L Sarda, A K A Silva, M Pocard, F Gazeau ACS Nano 2021
Photothermal Depletion of Cancer-Associated Fibroblasts Normalizes Tumor Stiffness in Desmoplastic Cholangiocarcinoma. A Nicolás-Boluda, J Vaquero, G. Laurent, G Renault, R Bazzi, E Donnadieu, S Roux, L Fouassier, F Gazeau ACS Nano 2020
Tumor stiffening reversion through collagen crosslinking inhibition favors T cell migration and enhances anti-PD-1 treatment. A Nicolas-Boluda, J Vaquero, S Barrin, C Kantari-Mimoun, M Ponzo, G Renault, P Deptuła, K Pogoda, R Bucki, I Cascone, J Courty, L Fouassier, F Gazeau, E Donnadieu eLife 2021
Two step promotion of a hot tumor immune environment by gold decorated iron oxide nanoflowers and light-triggered mild hyperthermia, A Nicolas-Boluda, G Laurent, R Bazzi, S Roux, E Donnadieu, F Gazeau Nanoscale 2021