Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles

Zhaohan Wei, Xiaoqiong Zhang, Tuying Yong, Nana Bie, Guiting Zhan, Xin Li, Qingle Liang, Jianye Li, Jingjing Yu, Gang Huang, Yuchen Yan, Zelong Zhang, Bixiang Zhang, Lu Gan (), Bo Huang () and Xiangliang Yang ()
Additional contact information
Zhaohan Wei: Huazhong University of Science and Technology
Xiaoqiong Zhang: Huazhong University of Science and Technology
Tuying Yong: Huazhong University of Science and Technology
Nana Bie: Huazhong University of Science and Technology
Guiting Zhan: Huazhong University of Science and Technology
Xin Li: Huazhong University of Science and Technology
Qingle Liang: Huazhong University of Science and Technology
Jianye Li: Huazhong University of Science and Technology
Jingjing Yu: Huazhong University of Science and Technology
Gang Huang: Huazhong University of Science and Technology
Yuchen Yan: Huazhong University of Science and Technology
Zelong Zhang: Huazhong University of Science and Technology
Bixiang Zhang: Huazhong University of Science and Technology
Lu Gan: Huazhong University of Science and Technology
Bo Huang: Peking Union Medical College
Xiangliang Yang: Huazhong University of Science and Technology

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8+ T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8+ T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20723-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20723-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20723-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().