TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy.
Christopher B. Rodell,Sean P. Arlauckas,Michael F. Cuccarese,Christopher Garris,Ran Li,Maaz S. Ahmed,Rainer H. Kohler,Mikael J. Pittet,Ralph Weissleder +8 more
TLDR
The ability of rationally engineered drug–nanoparticle combinations to efficiently modulate tumour-associated macrophages for cancer immunotherapy is demonstrated and R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro.Abstract:
Tumour-associated macrophages are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet, macrophages are highly plastic and can also acquire an anti-tumorigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNP-R848) lead to efficient drug delivery to tumour-associated macrophages in vivo. As a monotherapy, the administration of CDNP-R848 in multiple tumour models in mice altered the functional orientation of the tumour immune microenvironment towards an M1 phenotype, leading to controlled tumour growth and protecting the animals against tumour rechallenge. When used in combination with the immune checkpoint inhibitor anti-PD-1, we observed improved immunotherapy response rates, including in a tumour model resistant to anti-PD-1 therapy alone. Our findings demonstrate the ability of rationally engineered drug-nanoparticle combinations to efficiently modulate tumour-associated macrophages for cancer immunotherapy.read more
Citations
More filters
Journal ArticleDOI
In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment
Qian Chen,Qian Chen,Chao Wang,Xudong Zhang,Guojun Chen,Quanyin Hu,Quanyin Hu,Hongjun Li,Jinqiang Wang,Di Wen,Yuqi Zhang,Yifei Lu,Yifei Lu,Guang Yang,Chen Jiang,Jun Wang,Gianpietro Dotti,Zhen Gu +17 more
TL;DR: The findings indicate that the immunotherapeutic fibrin gel ‘awakens’ the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.
Journal ArticleDOI
Macrophage M1/M2 polarization.
TL;DR: The mechanism of macrophage polarization from the tumor microenvironment, nanocarriers, nuclear receptor PPARγ, phagocytosis, NF-κB signaling pathways, and other pathways is analyzed.
Journal ArticleDOI
Enhancing cancer immunotherapy with nanomedicine.
Darrell J. Irvine,Eric L. Dane +1 more
TL;DR: How nanomedicine-based treatment strategies are well suited to immunotherapy on the basis of nanomaterials’ ability to direct immunomodulators to tumours and lymphoid organs, to alter the way biologics engage with target immune cells and to accumulate in myeloid cells in tumour and systemic compartments is discussed.
Journal ArticleDOI
Improving cancer immunotherapy through nanotechnology.
TL;DR: How nanotechnology and related approaches are being applied to augmenting both endogenous leukocytes and adoptively transferred ones by informing specificity, influencing localization and improving function is explored.
Journal ArticleDOI
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
TL;DR: In this paper, the authors studied the impact of host-intrinsic factors (such as the host genome, epigenome, and immunity) on immune checkpoint blockade (ICB) response and toxicity.
References
More filters
Journal ArticleDOI
Cancer-related inflammation.
TL;DR: The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
Journal ArticleDOI
Macrophage plasticity and polarization: in vivo veritas
Antonio Sica,Alberto Mantovani +1 more
TL;DR: The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for Macrophage-centered diagnostic and therapeutic strategies.
Journal ArticleDOI
Cancer nanomedicine: progress, challenges and opportunities.
TL;DR: Novel engineering approaches are discussed that capitalize on the growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.
Journal ArticleDOI
The future of immune checkpoint therapy
Padmanee Sharma,James P. Allison +1 more
TL;DR: The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.
Related Papers (5)
Tumor-associated macrophages: from mechanisms to therapy.
CSF-1R inhibition alters macrophage polarization and blocks glioma progression
Stephanie M. Pyonteck,Leila Akkari,Alberto J. Schuhmacher,Robert L. Bowman,Lisa Sevenich,Daniela F. Quail,Oakley C. Olson,Marsha L. Quick,Jason T. Huse,Virginia Teijeiro,Manu Setty,Christina S. Leslie,Yoko Oei,Alicia Pedraza,Jianan Zhang,Cameron Brennan,James Sutton,Eric C. Holland,Dylan Daniel,Johanna A. Joyce +19 more
Understanding the tumor immune microenvironment (TIME) for effective therapy.
Mikhail Binnewies,Edward W. Roberts,Kelly Kersten,Vincent Chan,Douglas F. Fearon,Miriam Merad,Lisa M. Coussens,Dmitry I. Gabrilovich,Suzanne Ostrand-Rosenberg,Suzanne Ostrand-Rosenberg,Catherine C. Hedrick,Robert H. Vonderheide,Mikael J. Pittet,Rakesh K. Jain,Weiping Zou,T. Kevin Howcroft,Elisa C. Woodhouse,Robert A. Weinberg,Matthew F. Krummel +18 more