title: Epstein-Barr Virus-Induced Gene 3 (EBI3) Blocking Leads to Induce Antitumor Cytotoxic T Lymphocyte Response and Suppress Tumor Growth in Colorectal Cancer by Bidirectional Reciprocal-Regulation STAT3 Signaling Pathway.
abstract: Epstein-Barr virus-induced gene 3 (EBI3) is a member of the interleukin-12 (IL-12) family structural subunit and can form a heterodimer with IL-27p28 and IL-12p35 subunit to build IL-27 and IL-35, respectively. However, IL-27 stimulates whereas IL-35 inhibits antitumor T cell responses. To date, little is known about the role of EBI3 in tumor microenvironment. In this study, firstly we assessed EBI3, IL-27p28, IL-12p35, gp130, and p-STAT3 expression with clinicopathological parameters of colorectal cancer (CRC) tissues; then we evaluated the antitumor T cell responses and tumor growth with a EBI3 blocking peptide. We found that elevated EBI3 may be associated with IL-12p35, gp130, and p-STAT3 to promote CRC progression. EBI3 blocking peptide promoted antitumor cytotoxic T lymphocyte (CTL) response by inducing Granzyme B, IFN-γ production, and p-STAT3 expression and inhibited CRC cell proliferation and tumor growth to associate with suppressing gp130 and p-STAT3 expression. Taken together, these results suggest that EBI3 may mediate a bidirectional reciprocal-regulation STAT3 signaling pathway to assist the tumor escape immune surveillance in CRC.
authors.affiliation: Department of Pathology, Dongguan Hospital, Medical College of Jinan University, The Fifth People's Hospital of Dongguan, Dongguan 523905, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Pathology, Dongguan Hospital, Medical College of Jinan University, The Fifth People's Hospital of Dongguan, Dongguan 523905, China.
authors.forename: Can
authors.initials: C
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Yang
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pathology, Dongguan Hospital, Medical College of Jinan University, The Fifth People's Hospital of Dongguan, Dongguan 523905, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Kang
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Bihua
authors.initials: B
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Chai
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Keyuan
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D010455:Peptides / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C097732:EBI3 protein, human; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D050796:STAT3 Transcription Factor