Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles.

Autor: Son S; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. ssejin@inha.ac.kr.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. ssejin@inha.ac.kr.; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ssejin@inha.ac.kr.; Department of Biological Sciences, Inha University, Incheon, Republic of Korea. ssejin@inha.ac.kr.; Department of Biological Sciences and Bioengineering, Inha University/Industry-Academia Interactive R&E Center for Bioprocess Innovation, Inha University, Incheon, Republic of Korea. ssejin@inha.ac.kr., Nam J; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea., Kim AS; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Ahn J; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, Dongguk University, Seoul, Republic of Korea., Park KS; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Phoo MT; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Sherren B; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Zou W; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Lee SH; Department of Biomedical Engineering, Dongguk University, Seoul, Republic of Korea., Farokhzad OC; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Seer, Inc., Redwood City, CA, USA., Shi J; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Moon JJ; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. moon@med.umich.edu.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. moon@med.umich.edu.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. moon@med.umich.edu.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. moon@med.umich.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2023 Jan; Vol. 7 (1), pp. 72-84. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1038/s41551-022-00973-4
Abstrakt: The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (T H 17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates T H 17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce T H 17-cell-mediated anti-tumour responses. The nanoparticles activate the pattern-recognition receptor Dectin-2 and Toll-like receptor 4 in dendritic cells, and promote the differentiation of CD4 + T cells into the T H 17 phenotype. In mice, intra-tumoural administration of the nanoparticles decreased the fraction of regulatory T cells in the tumour while markedly increasing the fractions of T H 17 cells (and the levels of T H 17-cell-associated cytokines), CD8 + T cells, natural killer cells and M1-like macrophages. The anti-tumoural activity of the effector cells was amplified by an agonistic antibody against the co-stimulatory receptor OX40 in multiple mouse models. Nanomaterials that induce T H 17-cell-mediated immune responses may have therapeutic potential.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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