In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade

IF 2.9 4区 医学 Q2 CELL BIOLOGY
Kristian W. Antonsen , Anne G. Jensen , Boe S. Sorensen , Anders Etzerodt , Søren K. Moestrup , Holger J. Møller
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引用次数: 0

Abstract

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.
体外卵巢肿瘤条件CD163+人巨噬细胞对CD47阻断保持吞噬反应
表达cd163的巨噬细胞在卵巢癌中大量存在,它们加速肿瘤的生长和转移。CD47阻断是一种新的免疫疗法,旨在激活巨噬细胞吞噬肿瘤细胞,但目前尚不清楚表达CD163的肿瘤相关巨噬细胞是否对CD47阻断反应不良。方法将人单核细胞来源的巨噬细胞暴露于A2780卵巢癌细胞分化过程中的肿瘤条件培养基中。检测CD47阻断对A2780细胞基因表达、膜蛋白水平、可溶性蛋白释放和巨噬细胞吞噬的影响,并与对照巨噬细胞进行比较。结果肿瘤细胞调节诱导巨噬细胞在mRNA和蛋白水平上表达CD163。此外,肿瘤调节同时增加了表型标记CD206和CD80以及吞噬检查点LILRB1的蛋白表达。然而,肿瘤调节并没有降低吞噬能力,因为CD47阻断在对照和肿瘤细胞条件的巨噬细胞中诱导A2780细胞的吞噬程度相似。体外肿瘤调节并没有降低对CD47阻断的吞噬反应,这表明诱导巨噬细胞表型增加CD163的表达并不直接限制肿瘤细胞的吞噬能力。总之,这些发现表明CD163+巨噬细胞仍然对CD47阻断反应,突出了它们作为卵巢癌免疫治疗靶点的潜力。
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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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