title: Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+CD11b+ myeloid cells.
abstract: LM escape immune surveillance, in part, as a result of the expansion of CD11b+MC, which alter the intrahepatic microenvironment to promote tumor tolerance. HBC make up a significant proportion of liver lymphocytes and appear to delay tumor progression; however, their significance in the setting of LM is poorly defined. Therefore, we characterized HBC and HBC/CD11b+MC interactions using a murine model of LM. Tumor-bearing livers showed a trend toward elevated absolute numbers of CD19+ HBC. A significant increase in the frequency of IgM(lo)IgD(hi) mature HBC was observed in mice with LM compared with normal mice. HBC derived from tumor-bearing mice demonstrated increased proliferation in response to TLR and BCR stimulation ex vivo compared with HBC from normal livers. HBC from tumor-bearing livers exhibited significant down-regulation of CD80 and were impaired in inducing CD4(+) T cell proliferation ex vivo. We implicated hepatic CD11b+MC as mediators of CD80 down-modulation on HBC ex vivo via a CD11b-dependent mechanism that required cell-to-cell contact and STAT3 activity. Therefore, CD11b+MC may compromise the ability of HBC to promote T cell activation in the setting of LM as a result of diminished expression of CD80. Cross-talk between CD11b+MC and HBC may be an important component of LM-induced immunosuppression.
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, Rhode Island, USA; and Boston University School of Medicine, Boston, Massachusetts, USA mitchell.thorn@chartercare.org.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Thorn
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, Rhode Island, USA; and.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Point
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, Rhode Island, USA; and.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Burga
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, Rhode Island, USA; and.
authors.forename: Cang T
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, Rhode Island, USA; and Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: N
authors.initials: N
authors.lastname: Joseph Espat
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, Rhode Island, USA; and Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Katz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015536:Down-Regulation; D008113:Liver Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D008163:Luminescent Measurements / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039481:CD11b Antigen; D011956:Receptors, Cell Surface; C551746:granulocyte receptor 1, mouse
keywords: B cells; STAT3; immunosuppression; liver
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