A Theoretical Basis for the Efficacy of Cancer Immunotherapy and Immunogenic Tumor Dormancy: The Adaptation Model of Immunity

In the past decades, a variety of strategies have been explored to cure cancer by means of immunotherapy, which is less toxic compared with chemotherapy or radiation therapy, and could establish memory for long-lasting protection against tumor recurrence. These endeavors have been successful in offering therapeutic antibodies, vaccines, or cellular immunotherapies, which resulted in prolonging survival of some cancer patients; however, complete cures have not been consistently achieved. The conception, design, and implementation of these promising immunotherapeutic strategies have been influenced by two schools of thought in immunology, which include the "self-nonself" (SNS) model and the "danger" model. Further progress in cancer immunotherapy to achieve consistent cancer cures requires an evolution in our understanding of how the immune system works. The purpose of this review is to revisit premises and limitations of the SNS and danger models based on the outcomes of cancer immunotherapies by suggesting that both models are two sides of the same coin describing how the immune response is induced against cancer. However, neither explains how the immune response succeeds or fails in eliminating the tumor. To this end, the adaptation model has been proposed to explain efficacy of the immune response for achieving cancer cure.