Yazarlar : Zappasodi R, Bongarzone I, Ghedini GC, Castagnoli L, Cabras AD, Messina A, Tortoreto M, Tripodo C, Magni M, Carlo-Stella C, Gianni AM, Pupa SM, Di Nicola M.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21860023

Konu : Lenfoma

Literatür İçeriği :  

Abstract

We reported that the clinical efficacy of dendritic cell-based vaccination is strongly associated with immunological responses in relapsed B-cell non-Hodgkin lymphoma (B-NHL) patients. We have now investigated whether post-vaccination 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 pre-vaccination samples or non-responders' antibodies. Western blot analysis of DOHH-2 lymphoma proteome revealed a sharp band migrating at about 100-110 kDa only with post-vaccine repertoires from responders. Mass spectrometry identified heat shock protein (HSP) 105 in that molecular weight interval. Flow cytometry and immunohistochemistry disclosed HSP105 on the cell membrane and in the cytoplasm of B-NHL cells 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 anti-lymphoma 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 non-oncogenes that can be exploited as anti-lymphoma targets.

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