TY - JOUR
T1 - In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade
AU - Antonsen, Kristian Wiborg
AU - Jensen, Anne Grosbøl
AU - Sorensen, Boe
AU - Etzerodt, Anders
AU - Moestrup, Søren Kragh
AU - Møller, Holger Jon
PY - 2025/3/1
Y1 - 2025/3/1
N2 - Introduction: CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade. Methods: Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation. Effects on gene expression, membrane protein levels, release of soluble proteins and macrophage phagocytosis of A2780 cells in response to CD47 blockade were measured and compared to control macrophages. Results: Tumor cell conditioning induced macrophage expression of CD163 on both the mRNA and protein level. Furthermore, tumor conditioning simultaneously increased protein expression of the phenotype markers CD206 and CD80, and the phagocytosis checkpoint LILRB1. However, tumor conditioning did not reduce phagocytic capacity, as CD47 blockade induced macrophage phagocytosis of A2780 cells to similar degrees in both control and tumor cell-conditioned macrophages. Discussion: In vitro tumor conditioning did not reduce the phagocytic response to CD47 blockade, suggesting that induction of a macrophage phenotype with increased expression of CD163 does not directly limit the capacity for phagocytosis of tumor cells. In conclusion, these findings suggest that CD163+ macrophages remain responsive to CD47 blockade, highlighting their potential as targets for immunotherapy in ovarian cancer.
AB - Introduction: CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade. Methods: Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation. Effects on gene expression, membrane protein levels, release of soluble proteins and macrophage phagocytosis of A2780 cells in response to CD47 blockade were measured and compared to control macrophages. Results: Tumor cell conditioning induced macrophage expression of CD163 on both the mRNA and protein level. Furthermore, tumor conditioning simultaneously increased protein expression of the phenotype markers CD206 and CD80, and the phagocytosis checkpoint LILRB1. However, tumor conditioning did not reduce phagocytic capacity, as CD47 blockade induced macrophage phagocytosis of A2780 cells to similar degrees in both control and tumor cell-conditioned macrophages. Discussion: In vitro tumor conditioning did not reduce the phagocytic response to CD47 blockade, suggesting that induction of a macrophage phenotype with increased expression of CD163 does not directly limit the capacity for phagocytosis of tumor cells. In conclusion, these findings suggest that CD163+ macrophages remain responsive to CD47 blockade, highlighting their potential as targets for immunotherapy in ovarian cancer.
UR - http://www.scopus.com/inward/record.url?scp=85218270310&partnerID=8YFLogxK
U2 - 10.1016/j.cellimm.2025.104932
DO - 10.1016/j.cellimm.2025.104932
M3 - Journal article
C2 - 39985839
SN - 0008-8749
VL - 409-410
JO - Cellular Immunology
JF - Cellular Immunology
M1 - 104932
ER -