The relationship between cancer and the immune system is complicated but is the key to understanding the growing field of immunology and personalized medicine. Many cancers have already been demonstrated to respond to immunotherapy, including non-small cell lung, melanoma, renal, head and neck, Merkel cell, prostate, bladder, colon, Hodgkin lymphoma, and non-Hodgkin lymphoma.
Paul Monk, MD, an associate professor at the James Cancer Center at Ohio State University in Columbus, discussed the role of the immune system in cancer and considerations for immunotherapy during a session at the 41st Annual Congress in San Antonio, TX.
The immune system is responsible for either blocking tumor growth, development, and survival or allowing tumor outgrowth through a process of the three E’s.
- Elimination: The immune system eradicates cancer cells. This is a natural process involved with early disease.
- Equilibrium: The immune system controls the cancer cells. This occurs with later-stage tumors and represents a balanced dynamic between the immune system and cancer.
- Escape: The cancer cells evade the immune system. The tumor cell variants grow, resulting in progressive disease.
The key components involved in immune response are
- Molecules produced by microbes or foreign agents that bind to T cells and antibodies
- Antigen-presenting cells (APCs)
- Identify and uptake foreign antigens
- Present them to T cells
- T cells
- Activated by APCs
- Recognize and destroy cells containing foreign antigen
- B cells
- Produce antibodies specific to foreign antigens.
The specific features of an effective immune response are
- Specificity: the ability of the immune cells to identify and target specific antigen
- Trafficking: the ability of the activated immune system cells to migrate to particular antigens throughout the body
- Adaptability: allows for a broader immune response
- Target elimination: the ability of the immune cells to destroy the targeted cancer cells, usually via induction of apoptosis
- Durability (immune memory): the ability of the immune system to recognize an antigen to which it has previously been exposed and provide long-lasting protection against it.
Immunotherapy is an aspect of oncology treatment that has been gaining traction, as more than a dozen different agents have been approved by the U.S. Food and Drug Administration to target more than 10 different cancers. This treatment boosts or restores the ability of the immune system to fight cancer, infections, and other diseases. Examples of immunotherapies include monoclonal antibodies, cytokines, checkpoint inhibitors, and therapeutic vaccines. Immunotherapy also offers an options for combination therapy.
Research on immunotherapy has rapidly increased, with the number of abstracts presented at major conferences on this topic doubling between 2009 and 2012. Approximately 800 clinical trials studying immunotherapy agents are ongoing, with trials testing the agents both alone and in combination with conventional therapies.
Monk noted that the toxicities associated with immunotherapy should be managed cautiously. For mild toxicities, treatment should be held and a lower dose of steroids should be considered if no improvement is seen. For moderate to severe toxicities, treatment should be permanently discontinued and high-dose steroids should be used and tapered when symptoms improve. He noted the following recognized toxicities associated with immunotherapy.
- Abdominal pain
- Blood or mucus in stool
- Bowel perforation
- Abnormal liver function tests
- Unilateral or bilateral weakness
- Sensory alterations
- Mental status changes
- Abdominal pain
- Unusual bowel habits
- Abnormal thyroid function tests
Monk, P. (2016). Cancer immunotherapy review: Oncology perspective. Session presented at the ONS 41st Annual Congress, San Antonio, TX, April 28, 2016.