Combining in situ vaccination and immunogenic apoptosis to treat cancer

Immunization approaches are designed to stimulate the immune system and eliminate the tumor. Studies indicate that cancer immunization combined with certain chemotherapeutics and immunostimulatory agents can improve outcomes. Chemotherapeutics-based immunogenic cell death makes the tumor more recognizable by the immune system. In situ vaccination (ISV) utilizes established tumors as antigen sources and directly applies an immune adjuvant to the tumor to reverse a cold tumor microenvironment to a hot one. Immunogenic cell death and ISV highlight for the immune system the tumor antigens that are recognizable by immune cells and support a T-cell attack of the tumor cells. This review presents the concept of immunogenic apoptosis and ISV as a powerful platform for cancer immunization.The immune system recognizes and attacks tumors, but often the tumor is able to protect itself by generating a local immune suppressive environment that reduces antitumor immune response. Therapies such as immune checkpoint blockade antibodies are meant to overcome immune suppression and enable an effective antitumor immune response; however, many patients do not respond to immune checkpoint blockade therapy. Further immune manipulations are needed to improve the response to immune-based cancer treatments. Approaches that reverse the tumor-mediating immune suppression can be effective. This review discusses combining two such approaches, generating immunogenic cell death of tumor cells and treating recognized tumors with immune stimulatory reagents, called in situ vaccination or intratumoral immunotherapy.