Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines

Abstract

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

Figure 1.

Combined effects of chemotherapy and vaccine therapy on tumor immunity. Chemotherapy can enhance cancer vaccines in three ways: (1) Reducing tumor induced immune suppression; (2) Increasing tumor immunogenicity; (3) Directly stimulating the immune system to enhance effector T cells. Chemotherapy could condition both the immune system and the tumor so that cancer vaccines have the best chance of success. Cancer vaccines focus the immune response towards the cancer and will be most effective when tumor defenses are lowered.