Viral warriors: Unlocking the immune system’s potential with oncolytic viruses in cancer immunotherapy

Oncolytic viruses (OVs) represent an exciting avenue in tumor immunotherapy, harnessing the power of viruses to overcome resistance and enhance immune responses. OVs achieve this by selectively targeting and destroying tumor cells. This cell lysis releases tumor-specific antigens (TAAs), effectively creating an <i>in situ</i> vaccine that educates the immune system. Moreover, OVs directly trigger both innate and adaptive immunity and can be genetically engineered to secrete immune-boosting factors. Early studies have shown promising synergistic antitumor effects when OVs are combined with other cancer therapies or immunotherapies. A key advantage of OVs is their capacity to reprogram the tumor microenvironment (TME), transforming immunologically inert "cold" tumors into actively inflamed "hot" tumors. This environmental shift is crucial for successful immunotherapy, as it allows for increased infiltration of immune cells, particularly cytotoxic T lymphocytes (CTLs), into the tumor. This comprehensive review covers the history, mechanisms, and potential combinatorial strategies involving OVs. It also addresses the challenges faced in their development and highlights current clinical trials exploring their role as potent immunotherapeutic agents.