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Abstract
Oncolytic herpes simplex virus type 1 (HSV-1) strain RH2 induced immunogenic cell death (ICD) with the release and surface exposure of damage-associated molecular patterns (DAMPs) in squamous cell carcinoma (SCC) SCCVII cells. The supernatants of RH2-infected SCCVII cells also exhibited antitumor ability by intratumoral administration in SCCVII tumor-bearing mice. The supernatants of RH2-infected cells and mock-infected cells were concentrated to produce Med24 and MedC for proteomic analyses. In Med24, the up- and down-regulated proteins were observed. Proteins including filamin, tubulin, t-complex protein 1 (TCP-1), and heat shock proteins (HSPs), were up-regulated, while extracellular matrix (ECM) proteins were markedly down-regulated. Viral proteins were detected in Med 24. These results indicate that HSV-1 RH2 infection increases the release of danger signal proteins and viral gene products, but decreases the release of ECM components. These changes may alter the tumor microenvironment (TME) and contribute to enhancement of anti-tumor immunity against SCC.
Highlights
Oncolytic virotherapy is a novel therapeutic modality that directly induces the lysis of infected tumor cells, and subsequently enhances host immune responses [1,2,3,4]
Pathogen-associated molecular patterns (PAMPs) that exist in diverse organisms, but not in the host, provide exogenous signal regarding the presence of pathogens in the immune system, thereby promoting immunity [8,9]
We reported that an injection of oncolytic Herpes simplex virus type 1 (HSV-1) strain RH2 into squamous cell carcinoma cell (SCC) SCCVII tumors in inbred mice enhanced systemic anti-tumor immunity [14], and that cell death caused by RH2 was immunogenic cell death (ICD) with the release of damage-associated molecular patterns (DAMPs) such as ATP and high mobility group box 1 (HMGB1) [13]
Summary
Oncolytic virotherapy is a novel therapeutic modality that directly induces the lysis of infected tumor cells, and subsequently enhances host immune responses [1,2,3,4]. Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for the treatment of patients with solid tumors. Pathogen-associated molecular patterns (PAMPs) that exist in diverse organisms, but not in the host, provide exogenous signal regarding the presence of pathogens in the immune system, thereby promoting immunity [8,9]. Cells release damage-associated molecular patterns (DAMPs) as endogenous signals that alert the immune system to respond to unexpected cell death, microbial invasion, and stress [3,10]. Protein DAMPs include intracellular proteins such as high mobility group box 1 (HMGB1), heat shock protein (HSP), hyaluronic acid, calreticulin (CRT), and S100 protein [3,5]
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