Immunotherapy for cancer treatment represents a new approach to combating cancer. The well-established methods of treating cancer, including surgical removal, chemotherapy, radiation and targeted therapy are being complemented by increasingly advanced treatments. The principle of immunotherapy is based on the ability of the human immune system to recognize and fight cancer cells. By using specific therapies, cancer patients can be supported in their body’s own efforts to combat the disease. These cancer treatments have led to the growth and development of many types of cancer immunotherapies. PD-1 inhibitors are one such class of immunotherapy for treating several types of cancer.
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PD-1 Inhibitors, such as atezolizumab, interact with PD-1 receptors on the surface of T cells and block signaling that creates an environment that allows tumors to grow. In order to recognize cancer cells and attack them, T cells need to recognize and bind to the cancer cells. In some cases, cancer cells can hide from T cells by expressing proteins, such as PD-L1, that bind to PD-1 on T cells. The interaction between PD-1 and PD-L1 on cancer cells serves to switch T cells to a dormant or “suppressed” state. PD-1 inhibitors have been shown to block this interaction, thereby releasing T cells from dormancy and allowing them to recognize and attack cancer cells.
Understanding the Immune System and Cancer
The immune system consists of several parts that work together to fight off infections and other foreign objects that can cause harm to the body. Part of the immune system consists of immune cells that can recognize and eliminate abnormal cells. These abnormal cells can be caused by cancer. However, in many cases, the body’s immune cells are not able to recognize cancer cells. This is often the case with tumors, which can form when a group of abnormal cells grow together to form a mass.
In some cases, though, cancer cells can avoid being detected by the immune system and allow the tumor to grow. They achieve this by suppressing the activity of the immune cells, for example by decreasing the expression of molecules on the surface of cancer cells that would trigger an immune response. Immunotherapy is an established treatment approach for certain cancers and remains an active area of research.
What Is a PD-1 Inhibitor?
Immune checkpoint inhibitors, such as PD-1 inhibitors, are a form of cancer immunotherapy. PD-1 is expressed by T cells. Immune checkpoints, like PD-1, help control the immune response to prevent damage to healthy cells. Cancer cells can express proteins that bind to PD-1 and allow the cancer cells to evade immune destruction. PD-1 inhibitors block the binding of these proteins to PD-1 and allow the immune system to attack the cancer cells.
Tumor cells can cause immune cells to die or can stop them from growing and becoming active by making proteins that bind to PD-1. These drugs work by inhibiting the PD-1 interactions on the T cells and as a result enable the T cells to recognize the cancer cells. This leads to the ability of the immune system to attack and destroy the cancer cells in certain patients.
How PD-1 Inhibitors Work
For the immune system to function properly, there needs to be a balance of activation and control of the immune response. Checkpoint proteins, such as PD-1, help to control the immune system and maintain this balance.
Tumors can often switch on the PDL1 protein on their surface. PDL1 is the natural ligand for PD-1 and causes the immune system to switch off when it sees it. Some tumors cause an excess of PDL1 to be made by surrounding tissues to protect themselves from the immune system. PD-1 inhibitors can increase the activity of the immune system against cancer. PD-1 inhibitors work differently than chemotherapy, which kills rapidly dividing cells, and other targeted therapies that target specific abnormalities in cancer cells.
Because each of these treatments works differently, there are many clinical and/or other factors that will be considered by the treating doctor in determining the appropriate treatment option for a given patient.
Cancers That May Be Treated With PD-1 Inhibitors
Various studies and clinical trials investigated the use of PD-1 inhibitors to treat various types of cancers.
Cancers Treated with PD-1 Inhibitors:
- Melanoma
- Non-small cell lung cancer
- Head and neck cancers
- Kidney cancer
- Bladder cancer
- Esophageal cancer
- Gastric cancer
- Liver cancer
- Cervical cancer
- Hodgkin lymphoma
- Other selected cancers
Immunotherapy for various types of cancer and at different stages of the disease is available to a limited extent depending on regional treatment guidelines and individual circumstances.
Who May Be Eligible for Treatment?
Not every patient with cancer is a candidate for immunotherapy. Healthcare professionals evaluate several factors before recommending PD-1 inhibitors, including:
- Type of cancer
- Stage of disease
- Previous treatments
- Overall health
- Existing medical conditions
- Performance status
- Biomarker testing results
- Potential benefits and risks
Immunotherapy can be used as a single agent or in combination with other treatments, such as chemotherapy, targeted therapy, radiotherapy and surgery, depending on the clinical situation.
The Importance of Biomarker Testing
Biomarker testing has become an important part of treatment planning for many cancers. Laboratory testing may examine:
- PD-L1 protein expression
- Genetic alterations
- Tumor molecular characteristics
- Other biological markers associated with cancer
By understanding whether a patient may benefit from immunotherapy or not, test results can help guide a doctor in determining the appropriate treatment for an individual patient. Biomarker testing for immunotherapy represents a single component of a very complete evaluation of a patient with cancer and must be interpreted in the overall context of that patient’s medical history, and the current stage of the cancer in question, as well as imaging studies and other clinical information.
Potential Benefits of PD-1 Inhibitors
Clinical studies have evaluated the outcomes of PD-1 inhibitors in selected patients with certain cancers. Potential benefits may include:
- Improved immune recognition of cancer cells
- Durable responses in some patients
- Treatment options for selected advanced cancers
- Combination treatment opportunities
- More personalized treatment planning
Individual results vary greatly and therefore not every single patient will experience the same effects of treatment.
Possible Side Effects
As with all cancer treatments, PD-1 inhibitors can have side effects. Immune cells may become overactive and start to attack healthy tissues as well as cancer cells. Possible side effects may include:
- Fatigue
- Skin rash
- Itching
- Diarrhea
- Nausea
- Joint pain
- Changes in liver function tests
- Hormonal changes affecting endocrine glands
- Inflammation involving organs (pneumonitis, hepatis, enteritis, etc.) such as the lungs, liver, intestines, or thyroid.
Many adverse effects can be managed if they are recognized early. Thus, it is very important for patients to report any new or worsening symptoms to their healthcare providers in a timely manner. Evaluation and management of such symptoms can then be provided by the patients’ healthcare team.
The Role of Multidisciplinary Cancer Care
Cancer treatment often involves a team of healthcare professionals to manage the patient’s care. Depending on the patient’s condition, the care team may include:
- Medical oncologists
- Radiation oncologists
- Surgical oncologists
- Pathologists
- Radiologists
- Oncology nurses
- Pharmacists
- Nutrition specialists
- Supportive care professionals
Each specialist in turn can bring in their special knowledge, to enable an individualized treatment plan for the patient’s specific illness.
Ongoing Research
Research involving PD-1 inhibitors continues to expand. Current areas of investigation include:
- Earlier use of immunotherapy
- New combination treatment strategies
- Improved biomarker identification
- Personalized immunotherapy approaches
- Additional cancer types that may benefit
- Better understanding of treatment resistance
- Strategies to reduce immune-related side effects
Clinical trials continue to advance the understanding of how to incorporate immunotherapy into cancer treatment and identify patients who are most likely to benefit from these therapies.
Looking Ahead
Research continues to explore advances in biomarker testing, personalized medicine and new combination therapies for incorporating immunotherapy as treatment for more cancer types.
Concluding Thoughts
PD-1 inhibitors are an important type of cancer treatment for selected types of cancer. They work by switching off the ‘brake’ that is stopping the body’s natural cancer-killing immune cells from attacking cancer cells.
Because cancer is a diverse group of diseases, treatment decisions are individualized based on the type of cancer, the stage of the cancer, the patient’s biomarkers, the patient’s overall health, and the patient’s previous treatment. Patients with questions about immunotherapy and whether or not a PD-1 inhibitor would be appropriate for them should discuss their individual circumstances with their healthcare team.
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