title: Primary effusion lymphoma cell death induced by bortezomib and AG 490 activates dendritic cells through CD91.
abstract: To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients.
authors.affiliation: Department of Experimental Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, La Sapienza University, Rome, Italy. mara.cirone@uniroma1.it
authors.forename: Mara
authors.initials: M
authors.lastname: Cirone
authors.forename: Livia
authors.initials: L
authors.lastname: Di Renzo
authors.forename: Lavinia Vittoria
authors.initials: LV
authors.lastname: Lotti
authors.forename: Valeria
authors.initials: V
authors.lastname: Conte
authors.forename: Pankaj
authors.initials: P
authors.lastname: Trivedi
authors.forename: Roberta
authors.initials: R
authors.lastname: Santarelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Gonnella
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D037282:Calreticulin / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D054685:Lymphoma, Primary Effusion / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D021381:Protein Transport / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D037282:Calreticulin; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011719:Pyrazines; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000069286:Bortezomib