title: Fibroblast Activation Protein-α-Positive Fibroblasts Promote Gastric Cancer Progression and Resistance to Immune Checkpoint Blockade.
abstract: Gastric cancer (GC) is one of the main causes of cancer death. The tumor microenvironment has a profound effect on inducing tumor growth, metastasis, and immunosuppression. Fibroblast activation protein-α (FAP) is a protein that is usually expressed in fibroblasts, such as cancer-associated fibroblasts, which are major components of the tumor microenvironment. However, the role of FAP in GC progression and treatment is still unknown. In this study, we explored these problems based on GC patient samples and experimental models. We found that high FAP expression was an independent prognosticator of poor survival in GC patients. FAP+ cancer-associated fibroblasts (CAFs) promoted the survival, proliferation, and migration of GC cell lines in vitro. Moreover, they also induced drug resistance of the GC cell lines and inhibited the antitumor functions of T cells in the GC tumor microenvironment. More importantly, we found that targeting FAP+ CAFs substantially enhanced the antitumor effects of immune checkpoint blockades in GC xenograft models. This evidence highly suggested that FAP is a potential prognosticator of GC patients and a target for synergizing with other treatments, especially immune checkpoint blockades in GC.
authors.affiliation: Oncology Department, The 82nd Hospital of PLA, Huai'an City, Jiangsu Province, P.R. China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Wen
authors.affiliation: IMR Residency Program of Florida Hospital, Orlando, FL, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: He
authors.affiliation: Department of General Surgery, The 82nd Hospital of PLA, Huai'an City, Jiangsu Province, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiao
authors.affiliation: Department of Cardiology, The 82nd hospital of PLA, Huai'an City, Jiangsu Province, P.R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The 82nd Hospital of PLA, Huai'an City, Jiangsu Province, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Medical Institution, Nanjing University, Nanjing, P.R. China.
authors.forename: Xuequn
authors.initials: X
authors.lastname: Ren
authors.affiliation: Oncology Department, The 82nd Hospital of PLA, Huai'an City, Jiangsu Province, P.R. China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D010450:Endopeptidases; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D061026:Programmed Cell Death 1 Receptor; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha