Second, viruses carry ligands for pattern recognition receptors, which trigger the innate immune system 5. First, viruses introduce new antigens to the immune system, which are recognized by the host as foreign 5. This is mainly explained by three mechanisms. Viruses have a very high capacity to activate the innate and adaptive immune system. Effective induction of strong and sustained immune activation at the tumour sites would therefore be a promising therapeutic approach against cancer. Escape from immune surveillance is mainly explained by limited immune activation or tumour-induced immunosuppression within the microenvironment 2. Despite the physiological existence of these potent anticancer effector molecules, neoplastic cells can survive and expand in immune-competent individuals. In addition, cytokines such as tumour necrosis factor-α, interferon (IFN)-γ or type I IFN (IFN-I) can directly exert antiproliferative and pro-apoptotic effects on tumour cells, or indirectly, through modulation of the tumour microenvironment 1, 4. The immune system can directly attack tumour cells via antigen-specific cytotoxic CD8 + T cells, activated natural killer (NK) cells or antibody-mediated cytotoxicity 2, 3. Next to chemotherapy and targeted therapies, immunotherapy is one promising approach to treat cancer 1. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses.Įffective treatment of advanced tumours remains a major challenge because of limited availability of tumour-specific agents and development of drug resistance. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C + monocytes and additionally enhances tumour-specific CD8 + T cells. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity.
0 kommentar(er)
