In vitro 2D and 3D cancer models to evaluate compounds that modulate macrophage polarization.
Cell Immunol
; 378: 104574, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35764023
ABSTRACT
In vitro cancer models that can identify novel immunomodulating compounds are essential. Using a 3D multicellular tumor spheroid (MCTS) model comprising cancer cells, fibroblasts, and macrophages, we tested tumor-associated macrophage (TAM)-inhibiting compounds (CCL2 Ab, CSF1R inhibitor, CSF1R Ab) and TAM-reprograming compounds (poly IC, CD40 Ab, CD40 ligand) for their effects on monocyte infiltration and polarization in tumor spheroids. For characterization of macrophage polarization, we measured the expression of CD206, CD163, CD86, MHC II, CD40, and CD14 and measured 43 soluble factors in the 3D MCTS cultures. 2D macrophage models were evaluated for comparison. A CSF1R inhibitor prevented infiltration of monocytes into pancreatic cancer spheroids, and macrophages treated with the inhibitor showed decreased expression of M2 markers. Treatment with a CD40 ligand and poly IC induced M1 macrophage polarization in our models. We propose that these models can be used to improve the drug screening process of anti-cancer immunotherapies targeting macrophages.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ligante de CD40
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article