SPOTLIGHT Immunotherapy: Pushing the Frontier of Cancer Medicine The immune system is a complex network of cells (called white blood cells; see Sidebar 38, p. 100), tissues (e.g., bone marrow), organs (e.g., thymus), and the substances they make that help the body fight infections and other diseases, including cancer. The immune system actively detects threats from external (such as viruses and bacteria) and internal sources (such as abnormal or damaged cells) and works to eliminate them from the body. The immune system is highly effective in detecting and eliminating cancer cells, a process also known as cancer immune surveillance (417). However, as cancer cells acquire new properties during the course of disease progression (see Understanding the Path to Cancer Development, p. 24), some cells find ways to “hide” from the immune system, such as by decreasing or eliminating the numbers and/or amounts of proteins on the surface of tumor cells that are used by the immune system to recognize cancer cells; triggering certain brakes on immune cells that prevent them from eradicating cancer cells; and releasing molecules that weaken the ability of immune cells to detect and destroy cancer cells (418). Ongoing research is focused on better understanding how tumor cells evade the immune system and leveraging this knowledge to develop additional effective cancer treatments. Cancer Immunotherapy and How It Works Cancer immunotherapy refers to any treatment that works by using the immune system to fight cancer. The history of invoking the immune system to treat cancer dates back to the late 19th century, when William B. Coley, a surgeon in Memorial Hospital, New York, injected bacteria into patients with inoperable malignant cancers based on his observation that an infection appeared to have the side effect of shrinking tumors. He saw excellent responses in a fraction of more than 1,000 patients with cancer he treated, and these bacterial products became known as Coley's toxins (419). The use of Coley’s toxins was discontinued because of the risk of severe side effects, the emergence of radiotherapy and chemotherapy, and because scientists did not have the ability at that time to fully understand the mechanism by which they worked or failed. Over the past five decades, researchers have made unprecedented advances in understanding how the immune system detects and destroys cancer cells in the human body, which has reinvigorated the field of cancer immunology and has firmly established immunotherapy as the fifth pillar of cancer medicine (420). IN THIS SECTION, YOU WILL LEARN: ⚫ Cancer immunotherapeutics work by unleashing the power of a patient’s immune system to fight cancer and, over the last decade, have emerged as one of the most exciting new approaches to cancer treatment. ⚫ Immune checkpoint inhibitors (ICIs) work by releasing the brakes on the natural cancer-fighting power of the immune system. As of July 31, 2023, the FDA has approved 11 ICIs, and there is at least one ICI approved for treating 20 cancer types and for treating any type of solid tumors that share certain molecular characteristics. ⚫ CAR T-cell therapy provides more cancer-targeted immune cells called T cells. As of July 31, 2023, the FDA has approved six distinct CAR T-cell therapies for the treatment of a range of hematologic cancers. ⚫ T-cell engaging bispecific antibodies work by flagging cancer cells for destruction by the immune system. As of July 31, 2023, the FDA has approved six different T-cell engaging bispecific antibodies for the treatment of many cancers, including some extremely rare cancers. ⚫ Treatment with immunotherapeutics can lead to severe adverse effects and ongoing research is evaluating biomarkers that can identify patients who are most likely to respond to these treatments. ⚫ The new frontier of immunotherapy, which includes preventive and therapeutic vaccines, innovative cell therapies, novel checkpoint inhibitors, and a new age of treatment combinations, is poised to transform the future of clinical cancer care. AACR Cancer Progress Report 2023 99
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