Title | Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Wang Y, Song M, Liu M, Zhang G, Zhang X, Li MO, Ma X, J Zhang J, Huang X-Y |
Journal | Cell Rep |
Volume | 35 |
Issue | 1 |
Pagination | 108948 |
Date Published | 2021 Apr 06 |
ISSN | 2211-1247 |
Keywords | Animals, Antibodies, Antigens, Carrier Proteins, CD8-Positive T-Lymphocytes, Dendritic Cells, Drug Synergism, Immune Checkpoint Inhibitors, Immunity, Interferon-gamma, Interleukin-12, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Microfilament Proteins, Neoplasms, Programmed Cell Death 1 Receptor, Survival Analysis |
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. |
DOI | 10.1016/j.celrep.2021.108948 |
Alternate Journal | Cell Rep |
PubMed ID | 33826900 |
PubMed Central ID | PMC8050791 |
Grant List | P30 CA008748 / CA / NCI NIH HHS / United States R01 CA193815 / CA / NCI NIH HHS / United States |
Submitted by ljc4002 on August 21, 2025 - 3:23pm