Functional Gadofullerene Nanoparticles Trigger Robust Cancer Immunotherapy Based on Rebuilding an Immunosuppressive Tumor Microenvironment
- 10 June 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Nano Letters
- Vol. 20 (6), 4487-4496
- https://doi.org/10.1021/acs.nanolett.0c01287
Abstract
Cancer immunotherapy as a novel cancer therapeutic strategy has shown enormous promise. However, the immunosuppressive tumor microenvironment (ITM) is a primary obstacle. Tumor-associated macro-phages (TAMs) as a major component of immune cells in a tumor microenvironment are generally polarized to the M2 phenotype that not only accelerates tumor growth but also influences the infiltration of lymphocytes and leads to immunosuppression. Thus, rebuilding ITM by re-educating TAMs and increasing infiltration of lymphocytes is a promising strategy. Herein, gadofullerene (GF-Ala) nanoparticles are demonstrated to reprogram TAMs to M1-like and increase the infiltration of cytotoxic T lymphocytes (CTLs), achieving effective inhibition of tumor growth. Notably, the modulation of ITM by GF-Ala promotes the anticancer efficacy of anti-PD-L1 immune checkpoint inhibitor, achieving superior synergistic treatment. Additionally, GF-Ala nanoparticles can be mostly excreted from the body and cause no obvious toxicity. Together, this study provides an effective immunomodulation strategy using gadofullerene nanoparticles by rebuilding ITM and synergizing immune checkpoint blockade therapy.Funding Information
- Ministry of Science and Technology of the People's Republic of China (ZDYZ2015-2)
- Chinese Academy of Sciences (QYZDJ-SSW-SLH025)
This publication has 43 references indexed in Scilit:
- TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapyNature Biomedical Engineering, 2018
- The homeobox protein VentX reverts immune suppression in the tumor microenvironmentNature Communications, 2018
- Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotypeNature Communications, 2018
- De-novo and acquired resistance to immune checkpoint targetingThe Lancet Oncology, 2017
- Immune suppressive mechanisms in the tumor microenvironmentCurrent Opinion in Immunology, 2016
- Understanding Local Macrophage Phenotypes In Disease: Modulating macrophage function to treat cancerNature Medicine, 2015
- Macrophage biology in development, homeostasis and diseaseNature, 2013
- Alternative Activation of Macrophages: Mechanism and FunctionsImmunity, 2010
- Alternative Activation of Macrophages: An Immunologic Functional PerspectiveAnnual Review of Immunology, 2009
- Adoptive cell transfer: a clinical path to effective cancer immunotherapyNature Reviews Cancer, 2008