SPOTLIGHT Groundbreaking basic research in the field of immunology— the study of the immune system—has laid the foundation of modern immunotherapy, one of the most exciting new areas of cancer treatment along with molecularly targeted therapeutics (see Figure 15, p. 76). Cancer immunotherapeutics leverage the natural ability of the immune system to fight cancer (see Figure 17, p. 101) (421). There are various ways in which different immunotherapeutics unleash the immune system to fight cancer. Some immunotherapeutics work by unleashing the natural cancer-fighting powers of the immune system. Immune checkpoint inhibitors (ICIs) are examples of immunotherapeutics that work in this way. ICIs have revolutionized the landscape of cancer treatment and, over the past decade, have been approved widely by FDA for use in the treatment of diverse cancer types (see Releasing the Brakes on the Immune System, p. 101). Some immunotherapeutics dramatically amplify the cancer killing power of the immune system by either providing more Key Cells of the Immune System Cells of the immune system are made in the bone marrow and are called white blood cells. White blood cells work together to protect the body from external (such as pathogens) and internal (such as cancer cells) threats. Here, we briefly describe the unique functions of the white blood cells that have a central role in eliminating cancer. B cells make antibodies (e.g., against pathogens such as viruses and bacteria) that help eliminate pathogens as well as help other components of the immune system function. Some remain as memory B cells to make the same antibody again later, if needed. Understanding of the role of B cells in eliminating cancer is growing, but the ability of these cells to make antibodies that can be used to treat patients has been harnessed for several decades. T cells help protect the body from infection and can also help fight cancer. Some remain as memory T cells to fight again later. There are two main types of T cells based on a type of protein present on their surface: • CD4+ T cells help orchestrate the immune response. • CD8+ T cells kill infected, damaged, and abnormal cells, including cancer cells. Natural killer cells kill infected, damaged, and abnormal cells, including cancer cells. Dendritic cells educate T cells about what kinds of cells they should and should not attack. Macrophages eat foreign materials and can ingest and fight against cancer progression, but can also make molecules that help cancers grow. Mast cells release chemicals against pathogens and stimulate the immune system but can also provide factors that aid tumor growth and spread. Neutrophils are among the first immune cells to respond to external and internal threats, releasing chemicals that fight pathogens and stimulate the immune system. The effects of these cells can either fight against cancer progression or potentially help cancers grow. Basophils and eosinophils release chemicals against pathogens and stimulate the immune system. The effects of these cells can either help cancers grow or fight against cancer progression. Adapted from (9). SIDEBAR 38 COLEY’S TOXINS Coley’s toxins, widely considered one of the first examples of immunotherapy, are a mixture of toxins collected from certain types of bacteria. The mixture is named after William B. Coley, a surgeon at Memorial Hospital, New York, who developed the toxins in the late 19th century as a treatment for cancer (419). AACR Cancer Progress Report 2023 Immunotherapy: Pushing the Frontier of Cancer Medicine 100
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