IFN? is a central node of cancer immune equilibrium

Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune sys-tem. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. Using a non-replicating HSV-1 vector expressing interleukin-12 (d106S-IL12), we developed a mouse model of therapy-induced immune equilibrium, a phenomenon pre-viously seen only in humans. This immune equilibrium was centrally reliant on interferon-y (IFNy). CD8+ T cell direct recognition of MHC class I, perforin/granzyme-mediated cytotoxicity, and extrinsic death receptor signaling such as Fas/FasL were all individually dispensable for equilibrium. IFNy was critically important and played redundant roles in host and tumor cells such that IFNy sensing in either compartment was suffi-cient for immune equilibrium. We propose that these redundant mechanisms of action are integrated by IFNy to protect from oncogenic or chronic viral threats and establish IFNy as a central node in therapy-induced immune equilibrium.

Automated summary

Tumors in immune equilibrium are maintained by the immune system through the involvement of interferon-y (IFNy), which plays a critical role in protecting against oncogenic or chronic viral threats. IFNy is a central node in therapy-induced immune equilibrium.