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- Title
pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy.
- Authors
Tang, Mingmei; Chen, Binlong; Xia, Heming; Pan, Meijie; Zhao, Ruiyang; Zhou, Jiayi; Yin, Qingqing; Wan, Fangjie; Yan, Yue; Fu, Chuanxun; Zhong, Lijun; Zhang, Qiang; Wang, Yiguang
- Abstract
Tumour-associated macrophages (TAMs), as one of the most abundant tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, limiting an effective antigen cross-presentation. How to selectively reprogram M2-like TAMs to reinvigorate anti-tumour immune responses is challenging. Here, we report a pH-gated nanoadjuvant (PGN) that selectively targets the lysosomes of M2-like TAMs in tumours rather than the corresponding organelles from macrophages in healthy tissues. Enabled by the PGN nanotechnology, M2-like TAMs are specifically switched to a M1-like phenotype with attenuated lysosomal acidity and cathepsin activity for improved antigen cross-presentation, thus eliciting adaptive immune response and sustained tumour regression in tumour-bearing female mice. Our findings provide insights into how to specifically regulate lysosomal function of TAMs for efficient cancer immunotherapy. A high abundance of tumour associated macrophages with immunosuppressive properties is associated with inefficient anti-tumour immune responses. Here the authors report the design and characterization of pH-gated nanoparticles selectively targeting and reprogramming M2-like macrophages in the tumour microenvironment, re-sensitizing tumours to immune checkpoint blockade.
- Subjects
TUMOR-infiltrating immune cells; PROGRAMMED cell death 1 receptors; MACROPHAGES; IMMUNE response; IMMUNOTHERAPY; IMMUNE checkpoint proteins
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-41592-0