Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity Journal Article
| Authors: | Wang, Y.; Song, M.; Liu, M.; Zhang, G.; Zhang, X.; Li, M. O.; Ma, X.; Zhang, J. J.; Huang, X. Y. |
| Article Title: | Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity |
| Abstract: | Fascin protein is the main actin-bundling protein in filopodia and invadopodia, which are critical for tumor cell migration, invasion, and metastasis. Small-molecule fascin inhibitors block tumor invasion and metastasis and increase the overall survival of tumor-bearing mice. Here, we report a finding that fascin blockade additionally reinvigorates anti-tumor immune response in syngeneic mouse models of various cancers. Fascin protein levels are increased in conventional dendritic cells (cDCs) in the tumor microenvironment. Mechanistically, fascin inhibitor NP-G2-044 increases the number of intratumoral-activated cDCs and enhances the antigen uptake by cDCs. Furthermore, together with PD-1 blocking antibody, NP-G2-044 markedly increases the number of activated CD8+ T cells in the otherwise anti-PD-1 refractory tumors. Reduction of fascin levels in cDCs, but not fascin gene knockout in tumor cells, mimics the anti-tumor immune effect of NP-G2-044. These data demonstrate that fascin inhibitor NP-G2-044 simultaneously limits tumor metastasis and reinvigorates anti-tumor immune responses. © 2021 The Author(s) |
| Keywords: | controlled study; human tissue; unclassified drug; overall survival; nonhuman; cancer patient; pancreas cancer; flow cytometry; antineoplastic agent; cd8+ t lymphocyte; mass spectrometry; protein analysis; animal cell; mouse; animal tissue; cancer immunotherapy; metastasis; breast cancer; animal experiment; animal model; cohort analysis; lung cancer; in vivo study; antineoplastic activity; immunofluorescence; prostate cancer; patient care; dendritic cells; immune response; antigen; gamma interferon; tumor cell; cell isolation; tumor immunity; liver cancer; cell count; kidney cancer; cell activation; interleukin 12; immunocompetent cell; bioaccumulation; cell transfer; fascin; programmed death 1 ligand 1; tumor microenvironment; il-12; immune checkpoint inhibitor; fluorescence intensity; human; male; female; priority journal; article; anti-pd-1; tertiary lymphoid structure; cell migration assay; bone marrow derived dendritic cell; interferon gamma; gene knockout; antigen uptake; fascin inhibitors; np g2 044 |
| Journal Title: | Cell Reports |
| Volume: | 35 |
| Issue: | 1 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2021-04-06 |
| Start Page: | 108948 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2021.108948 |
| PUBMED: | 33826900 |
| PROVIDER: | scopus |
| PMCID: | PMC8050791 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 May 2021 -- Source: Scopus |
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