Immunotherapy of endometrial cancer via CD47 blockade-mediated macrophage phagocytosis

被引：0

作者：

Yucebas, Kerem ^{[1
]}

Ko, Sooah ^{[1
]}

Zhou, Jinyu ^{[1
]}

Hamel, Elizabeth M. ^{[1
]}

Hackworth, Mia G. ^{[1
,2
]}

Diaz Miranda, Edgar Andres ^{[1
]}

Carpenter, Haley S. ^{[1
]}

Hunter, Mark, I ^{[1
]}

Khan, Omair M. ^{[3
,4
]}

Weissman, Irving L. ^{[3
,4
]}

Jin, Shiying ^{[1
]}

机构：

[1] Univ Missouri, Sch Med, Dept Obstet Gynecol & Womens Hlth, Columbia, MO 65211 USA

[2] Univ Missouri, Coll Arts & Sci, Columbia, MO 65211 USA

[3] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

来源：

PNAS NEXUS | 2025年 / 4卷 / 05期

基金：

美国国家卫生研究院;

关键词：

CD47; macrophage; phagocytosis; immunotherapy; endometrial cancer; Biological Sciences; Medical Sciences; PROTEIN; RITUXIMAB; IMMUNITY; TARGET; CELLS;

D O I：

10.1093/pnasnexus/pgaf143

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The interaction between CD47 expressed on cancer cells and signal regulatory protein-alpha located on macrophages blocks the phagocytosis of tumor cells by macrophages. Our data reveal that human endometrial cancer cells (hECCs) upregulate the CD47 level on their surface and that there is a high density of tumor-associated macrophages within the microenvironment of human endometrial cancer. In vitro functional assay shows that an anti-CD47 monoclonal antibody (mAb) promotes the phagocytosis of hECCs by macrophages. Systemic and in situ treatments with an anti-CD47 mAb effectively reduce tumor burden in vivo in a genetically engineered mouse model of endometrial cancer. Thus, this study provides preclinical evidence that CD47 blockade using an anti-CD47 mAb to augment macrophage phagocytosis is a potential therapeutic strategy for endometrial cancer.

引用

页数：11

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