title: Immunogenic cell death by oncolytic herpes simplex virus type 1 in squamous cell carcinoma cells.
abstract: Molecules essential for the induction of immunogenic cell death (ICD) are called damage-associated molecular patterns (DAMPs). The effects of oncolytic herpes simplex virus type 1 (HSV-1) on the production of DAMPs were examined in squamous cell carcinoma (SCC) cells. The cytopathic effects of HSV-1 RH2 were observed in mouse SCCVII cells infected at a high multiplicity of infection (MOI), and the amounts of viable cells were decreased. After being infected with RH2, ATP and high mobility group box 1 (HMGB1) were released extracellulary, while calreticulin (CRT) translocated to the cell membrane. A flow-cytometric analysis revealed an increase in the number of annexin-V and propidium iodide (PI)-stained cells; and the amount of cleaved poly (ADP-ribose) polymerase (PARP) was increased. The killing effect of RH2 was reduced by pan-caspase inhibitor z-VAD-fmk and the caspase-1 inhibitor z-YVAD-fmk, suggesting the involvement of apoptosis and pyroptosis. In C3H mice bearing synergic SCCVII tumors, the growth of tumors injected with the supernatant of RH2-infected cells was less than that of tumors injected with phosphate-buffered saline (PBS). These results indicate that oncolytic HSV-1 RH2 produces DAMPs from SCC cells to induce cell death. This may contribute to the enhancement of tumor immunity by oncolytic HSV-1.
authors.affiliation: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Takasu
authors.affiliation: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Masui
authors.affiliation: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hamada
authors.affiliation: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.affiliation: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yura
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D037282:Calreticulin / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016923:Cell Death / Q000276:immunology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000276:immunology*; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000276:immunology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D037282:Calreticulin; D024243:HMGB1 Protein; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases