title: Serological identification of HSP105 as a novel non-Hodgkin lymphoma therapeutic target.
abstract: We reported that the clinical efficacy of dendritic cell-based vaccination is strongly associated with immunologic responses in relapsed B-cell non-Hodgkin lymphoma (B-NHL) patients. We have now investigated whether postvaccination antibodies from responders recognize novel shared NHL-restricted antigens. Immunohistochemistry and flow cytometry showed that they cross-react with allogeneic B-NHLs at significantly higher levels than their matched prevaccination samples or nonresponders' antibodies. Western blot analysis of DOHH-2 lymphoma proteome revealed a sharp band migrating at approximately 100 to 110 kDa only with postvaccine repertoires from responders. Mass spectrometry identified heat shock protein-105 (HSP105) in that molecular weight interval. Flow cytometry and immunohistochemistry disclosed HSP105 on the cell membrane and in the cytoplasm of B-NHL cell lines and 97 diagnostic specimens. A direct correlation between HSP105 expression and lymphoma aggressiveness was also apparent. Treatment of aggressive human B-NHL cell lines with an anti-HSP105 antibody had no direct effects on cell cycle or apoptosis but significantly reduced the tumor burden in xenotransplanted immunodeficient mice. In vivo antilymphoma activity of HSP105 engagement was associated with a significant local increase of Granzyme B(+) killer cells that very likely contributed to the tumor-restricted necrosis. Our study adds HSP105 to the list of nononcogenes that can be exploited as antilymphoma targets.
authors.affiliation: C. Gandini Medical Oncology, Bone Marrow Transplantation Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Zappasodi
authors.forename: Italia
authors.initials: I
authors.lastname: Bongarzone
authors.forename: Gaia C
authors.initials: GC
authors.lastname: Ghedini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Castagnoli
authors.forename: Antonello D
authors.initials: AD
authors.lastname: Cabras
authors.forename: Antonella
authors.initials: A
authors.lastname: Messina
authors.forename: Monica
authors.initials: M
authors.lastname: Tortoreto
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Michele
authors.initials: M
authors.lastname: Magni
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Serenella M
authors.initials: SM
authors.lastname: Pupa
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000937:Antigen-Antibody Reactions; D045744:Cell Line, Tumor; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D012698:Serologic Tests; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000906:Antibodies; D050957:HSP110 Heat-Shock Proteins; C097205:HSPH1 protein, human