Oncolytic Herpes Simplex Virus-susceptible tumor cell phenotype

This target refers to a specific cellular phenotype characterized by the loss of innate antiviral defenses and the presence of viral entry mediators, which together facilitate selective infection by oncolytic Herpes Simplex Viruses (oHSVs) [1, 2]. Many cancers dysregulate the Type I Interferon (IFN) signaling pathway—through mutations or epigenetic silencing of components like STING, cGAS, or JAK/STAT—to avoid immune-mediated growth arrest and apoptosis [4]. This defect creates a permissive environment where oHSVs can replicate without being suppressed by the host cell's antiviral response. Simultaneously, the expression of entry receptors such as Nectin-1 (CD111) and Herpesvirus Entry Mediator (HVEM) on the tumor cell surface allows for efficient viral binding and internalization [2, 3]. Therapeutic agents like Talimogene laherparepvec (T-VEC) exploit this phenotype to achieve tumor-selective lysis while inducing a systemic anti-tumor immune response through the release of progeny virions and tumor antigens [1, 5]. This dual-mechanism approach results in direct oncolysis and the stimulation of an abscopal effect, targeting both injected and non-injected lesions.

Other names

Tumor cells with dysregulated interferon signaling and tumor-associated HSV entry receptorsIFN-deficient tumor cellsHSV-sensitive cancer cellsoHSV-permissive tumor cells

Selective viral replication within IFN-deficient cells leading to direct oncolysis and stimulation of systemic anti-tumor immunity via antigen release and GM-CSF expression.