25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap

In 1909, Paul Ehrlich first suggested that the immune system is critical for suppressing carcinogenesis and cancer growth, which led to the introduction of cancer immunosurveillance by Sir MacFarlane Burnet in 1960. Burnet’s cancer immunosurveillance was further supported and elaborated by Thomas Lewis in 1982, who noted, for example, the limitations of investigating cancer immunosurveillance in available experimental models, except for virus-induced cancers. The concept of cancer immunosurveillance in 2001 was revised to cancer immunoediting (the immunoediting term was introduced by Dr. Rober Schreiber), based on findings that the immune system not only controls tumorigenesis and tumor growth but also tumor quality/grade or immunogenicity. Advances in immunology, including the identification of target organs and the local immune system, and the identification of novel innate immune cells regulating the adaptive immune response, have further advanced the understanding of cancer immunosurveillance and immunoediting. The current article discusses the evolution of the cancer immunosurveillance hypothesis into cancer immunoediting. At the time of the introduction of cancer immunoediting, the direct role of dendritic cells (DCs) in tumor immunity and immunoediting was not much explored. Similarly, the concept of tumor-associated macrophages (TAMs) and their role in cancer immunosurveillance and immunoediting was not much studied. The current article discusses the evolution of DCs and TAMs in the context of tumor immunity, cancer immunoediting, and immunotherapies specifically targeting these innate immune cells.