The role of immunogenic clinical death in the virotherapy of malignant neoplasms

Abstract

The work considers the main directions, results of experimental and clinical researches of a role of immunogenic cell death in verotherapy of malignant neoplasms. Cell death under the influence of oncolytic viruses, which occurred in the scenario of immunogenic cell death with the release of dangerously associated molecular patterns, was estimated. Clinical cases were divided by us into 2 types according to the method of activating the stress agent of the endoplasmic reticulum. Precisely those that influenced directly on structures inside the cell besides the endoplasmic reticulum, launching its stress indirectly through targets such as cytoplasmic proteins, membrane proteins and channels, proteins of the DNA replication system, and those that launched endoplasmic reticulum stress acting directly on the endoplasmic reticulum and breaking its work. The influence of oncolytic viruses on cells of malignant neoplasms is estimated. In our opinion, a significant positive difference between oncolytic viruses and other inducers of immunogenic cell death is that the infected cell with oncolytic viruses secretes pathogen-associated molecular patterns, which are structural molecules and waste products. Such additional stimulation may enhance the activity of immunocytes and increase the efficiency of antigen presentation. We have observed that cells with low-affinity T-cell receptors can escape negative selection, but their activity is usually insufficient to launch a full immune response due to the immunosuppressive microenvironment in the tumor. Immunogenic cell death may oppress this immunosuppression and increase the activity of the low-affinity clone of T lymphocytes for some time, but after the attenuation of immunogenic cell death, this pool is rapidly suppressed by the peripheral tolerogenic mechanisms and immunological memory hardly develops. In our opinion, this is especially actual for chemotherapeutic treatment regimens, because they have a limited duration due to the development of side effects. A detailed analysis of our own research and literature data allow to mention that oncolytic viruses seem to be an effective solution as an inducer of immunogenic cell death - they multiply in the tumor and cause immunogenic cell death for a long time while they are able to infect other tumor cells, which сonsequently allow recommending them as a stage of combined treatment of patients with oncopathology. Keywords: oncology, cell death, immunogenic apoptosis, oncolytic viruses.