Fibroblast activation proteins-α suppress tumor immunity by regulating T cells and tumor-associated macrophages.

Abstract

Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in >90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment. However, the effect of FAPα on Tregs and TAMs is unknown. The non-enzymatic function of FAPα on Treg and TAM was investigated. In this study, we confirm that FAPα can promote the generation of Tregs and TAMs, which suggests that FAPα plays a immunosuppressive role in the tumor microenvironment and provides evidence for FAP α as a potent immunotherapeutic target for cancer.

• Authors: Chun Mei Hou, Xue Mei Qu, Jian Zhang, Ting Ting Ding, Wei Han, Guang Chuan Ji, Zhao Hua Zhong, He Chen, FengMin Zhang
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 104 Issue 1 Pg. 29-37 (02 2018) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 29273462 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD163 antigen
• CD68 antigen, human
• FOXP3 protein, human
• Forkhead Transcription Factors
• Membrane Proteins
• Receptors, Cell Surface
• Endopeptidases
• Serine Endopeptidases
• fibroblast activation protein alpha
• Gelatinases

Topics

• Animals
• Antigens, CD (biosynthesis, immunology)
• Antigens, Differentiation, Myelomonocytic (biosynthesis, immunology)
• Cancer-Associated Fibroblasts (immunology)
• Carcinoma, Ovarian Epithelial
• Cell Differentiation (immunology)
• Cell Line, Tumor
• Coculture Techniques
• Endopeptidases
• Female
• Forkhead Transcription Factors (biosynthesis, immunology)
• Gelatinases (biosynthesis, immunology)
• Humans
• Macrophages (immunology)
• Membrane Proteins (biosynthesis, immunology)
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Neoplasms, Glandular and Epithelial (immunology)
• Ovarian Neoplasms (immunology)
• Primary Cell Culture
• Receptors, Cell Surface (biosynthesis, immunology)
• Serine Endopeptidases (biosynthesis, immunology)
• T-Lymphocytes, Regulatory (immunology)
• Tumor Microenvironment (immunology)