Immunotherapy Overview

For decades, doctors and researchers have conducted clinical trials to further progress in the clinical implementation of tumor immunotherapy. Former President Jimmy Carter’s success with immunotherapy for advanced melanoma and Vice President Joe Biden’s Cancer Moonshot Initiative have brought this new treatment type, as well as cancer treatments in general, into the spotlight for the general public. As a result, health care professionals may experience a spike in inquiries about this new treatment.

Several immunotherapy agents are now available for melanoma. Although surgery often remains the first line of treatment, especially for early-stage melanomas, the U.S. Food and Drug Administration (FDA) is rapidly approving new immunotherapy medications for advanced melanoma.

What is Immunotherapy?

Immunotherapy is a type of treatment that uses the body’s own immune system to recognize and kill cancer cells. Cancer cells often can fool the body into not recognizing they are dangerous. If the body can’t tell the difference between cancer cells and healthy cells, cancer cells may be able to “hide” from the immune system. To identify cancer cells as a threat and target them for destruction, immunotherapy uses substances either made by the body or in a laboratory to enhance recognition or effector function of the immune response against the cancer.

Different types of immunotherapy exist. Each works in a unique way to slow and stop the growth of cancer cells, stop cancer cells from spreading to other parts of the body and help the immune system work better overall at destroying cancer cells. Some immunotherapy treatments boost the body’s immune system while others train the immune system to attack cancer cells:

  • Checkpoint inhibitors are an important part of the immune system due to their ability to keep immune cells from attacking normal cells in the body. Checkpoints are proteins on immune cells that need to be turned on or off to start/stop an immune response. The immune system uses checkpoints to prevent itself from attacking normal cells in the body and deleted immune cells after their functions have been completed, for example following clearance of an infection. But melanoma cells sometimes hijack these checkpoints to avoid being attacked by the immune system. Checkpoint inhibitors target the checkpoint proteins, helping to restore the immune response against melanoma cells.
  • Cytokines are soluble molecules that enable immune cells to communicate with each other. Cytokines work together to make sure that the immune response is of the right strength and length of time.  Laboratory-made versions of cytokines are sometimes used to boost the immune system in people with melanoma.
  • Oncolytic viruses are viruses altered in a laboratory so that they preferentially infect and kill mainly cancer cells. Along with killing the cells directly, the viruses can also alert the immune system to attack the cancer cells.
  • Cancer vaccines are substances that stimulate the immune system to fight infection or disease. Cancer vaccines strengthen the immune system against cancer cells.
  • Nonspecific immune stimulators boost the immune system in a general way to help the immune system attack cancer cells.

Certain immunotherapies work well when given alone. Others work better in combination with additional treatment strategies.

At present, the clinical use of immunotherapy is largely restricted to the adjuvant treatment of Stage III and systemic treatment of Stage IV melanomas, although there is intense interest in evaluating immunotherapy as neoadjuvant or adjuvant therapy for all stages.

Why is Immunotherapy in Demand?

Immunotherapy has the potential to achieve durable clinical responses in some patients. In addition, an improved quality of life may also make immunotherapy an attractive choice for people who have this treatment option. Immunotherapy may be an option for patients to consider because the side effects, although prevalent, may be easier on patients compared to typical chemotherapy-related toxicities, and with appropriate attention, can be simple to manage. The side effect profile differs from other types of cancer therapeutics. Some side effects occur as a result of an overactive immune system, not the destruction of healthy cells, as often occurs with cytototoxic chemotherapy. Because not as many healthy cells are damaged with immunotherapy, some patients have reported a different range of side effects.

One limitation to immunotherapy is that it can be very effective in some patients but not in others. Researchers continue to explore why this happens to determine how to improve existing therapies and to develop new ones through clinical trials. Researchers are interested in identifying biomarkers that may be able to better predict which patients are likely to respond to which immunotherapy agents or combinations.

Several immunotherapy agents or regimens are currently approved by the FDA for the treatment of melanoma. Other novel treatments that are not yet FDA-approved may be accessible through clinical trials. Discuss the opportunity to participate in a clinical trial with your patients if they have not responded to other therapies or if you feel this may be the best treatment option for them. Provide them with multiple resources, and encourage them to become advocates for their own health by learning about and researching available clinical trials. A menu of active melanoma immunotherapy trials can be found at

A Long History

Overview_William_Coley.jpgCancer treatments are not discovered overnight. More than a century ago, Dr. William B. Coley worked with doctors and people with cancer to study how cancer tumors reacted to bacterial infections. His treatments for people with inoperable tumors consisted of injecting a combination of bacteria directly into the tumors. The treatment shrank the tumors and sometimes even led to a cure. Dr. Coley believed the body’s increased response to the bacteria also helped fight off the cancer.

More recently, in the 1960s, Dr. Donald Morton began experimenting with a vaccine that was intended not to prevent cancer but to stimulate the body’s immune system to attack cancer cells once they had developed. An early proponent of immunotherapy, particularly cancer vaccines, Dr. Morton was at the forefront of global cancer research and treatment, with a focus on melanoma. His work with bacillus Calmette-Guerin (BCG) for melanoma led to the approval of BCG for bladder cancer, the first successful immunotherapy against a human tumor.

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SITC Resources

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The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights of the latest advances in immunotherapy emerging from the ESMO Congress 2019 held in Barcelona, Spain. SITC CONNECT Account A SITC Cancer Immunotherapy CONNECT account is required to view past meeting highlights.  Click ...
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Adrenocortical carcinoma (ACC) is a rare malignancy without good treatment options. There are limited data about the use of immunotherapy in ACC. The authors investigated the efficacy and safety of pembrolizumab in patients with metastatic ACC. They concluded that single-agent pembrolizumab has modest ...
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Immune checkpoint inhibitors (ICIs) confer a survival benefit in many cancer types. Given that the survival outcome for cancer of unknown primary site (CUP) remains poor, the authors investigated the potential of CUP for immunotherapy. The authors conclude that the survival outcome of CUP remains unsatisfactory. ...
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The authors present  a case of sequential immune-related adverse events (irAEs) in a patient with metastatic melanoma treated with single-agent anti-programmed cell death-1 (PD-1) therapy, pembrolizumab. Although numerous cases of irAEs have been reported, sequential multi-organ involvement, including ...
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Hypophysitis is a well-recognized immune-related adverse event in patients treated with immune checkpoint inhibitors for cancer. Some anterior pituitary hormones may recover; however, secondary adrenal insufficiency is usually permanent. This case documents an unusual recovery from secondary adrenal ...