M. Panagi, F. Mpekris, P. Chen, C. Voutouri, Y. Nakagawa, J. D. Martin, T. Hiroi, H. Hashimoto, P. Demetriou, C. Pierides, R. Samuel, A. Stylianou, C. Michael, S. Fukushima, P. Georgiou, P. Papageorgis, P. Ch. Papaphilippou, L. Koumas, P. Costeas, G. Ishii, M. Kojima, K. Kataoka, H. Cabral, T. Stylianopoulos
Nat. Commun. 13, (2022) (DOI: 10.1038/s41467-022-34744-1)
Our paper entitled “Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models” has been published on Nature Communications and highlighted by media:
▶ Investigación y Ciencia
▶ The University of Tokyo Press Release
▶ EurekAlert!
▶ PHYS-ORG News
▶ Today’s Chronic
Abstract:
Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.
