title: Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model.
abstract: Unlike heterogeneous tumor cells, cancer-associated fibroblasts (CAF) are genetically more stable which serve as a reliable target for tumor immunotherapy. Fibroblast activation protein (FAP) which is restrictively expressed in tumor cells and CAF in vivo and plays a prominent role in tumor initiation, progression, and metastasis can function as a tumor rejection antigen. In the current study, we have constructed artificial FAP(+) stromal cells which mimicked the FAP(+) CAF in vivo. We immunized a breast cancer mouse model with FAP(+) stromal cells to perform immunotherapy against FAP(+) cells in the tumor microenvironment. By forced expression of FAP, we have obtained FAP(+) stromal cells whose phenotype was CD11b(+)/CD34(+)/Sca-1(+)/FSP-1(+)/MHC class I(+). Interestingly, proliferation capacity of the fibroblasts was significantly enhanced by FAP. In the breast cancer-bearing mouse model, vaccination with FAP(+) stromal cells has significantly inhibited the growth of allograft tumor and reduced lung metastasis indeed. Depletion of T cell assays has suggested that both CD4(+) and CD8(+) T cells were involved in the tumor cytotoxic immune response. Furthermore, tumor tissue from FAP-immunized mice revealed that targeting FAP(+) CAF has induced apoptosis and decreased collagen type I and CD31 expression in the tumor microenvironment. These results implicated that immunization with FAP(+) stromal cells led to the disruption of the tumor microenvironment. Our study may provide a novel strategy for immunotherapy of a broad range of cancer.
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Mingyao
authors: M
authors: Meng
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Wenju
authors: W
authors: Wang
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.
authors: Jun
authors: J
authors: Yan
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.
authors: Jing
authors: J
authors: Tan
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.
authors: Liwei
authors: L
authors: Liao
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Jianlin
authors: J
authors: Shi
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Chuanyu
authors: C
authors: Wei
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Yanhua
authors: Y
authors: Xie
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Xingfang
authors: X
authors: Jin
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.
authors: Li
authors: L
authors: Yang
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.
authors: Qing
authors: Q
authors: Jin
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.
authors: Huirong
authors: H
authors: Zhu
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China.
authors: Weiwei
authors: W
authors: Tan
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China. yangfangkm@126.com.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China. yangfangkm@126.com.|Kunming Medical University, Kunming, 650050, Yunnan, People's Republic of China. yangfangkm@126.com.
authors: Fang
authors: F
authors: Yang
authors: Department of Central Laboratory, Yan'an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunnan, People's Republic of China. hzl579@163.com.|Yunnan Cell Biology and Clinical Translation Research Center, Kunming, 650051, Yunnan, People's Republic of China. hzl579@163.com.
authors: Zongliu
authors: Z
authors: Hou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D018093:Gelatinases / Q000276:immunology*; D007114:Immunization; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012697:Serine Endopeptidases / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
keywords: Breast cancer model; Cancer-associated fibroblast; Fibroblast activation protein; Immunotherapy; Tumor microenvironment