Immunotherapy is a cancer treatment that enhances the body’s own immune system to target and eliminate cancer cells, rather than attacking the cancer with external agents. These therapies work by manipulating the cellular machinery that regulates immune responses, training immune cells to fight the disease more efficiently. Unlike chemotherapy or radiation, this approach empowers the patient’s internal systems to act against the malignancy.
How Anti-PD-1 Drugs Activate the Immune System
The immune system has natural regulators called checkpoints, which are proteins on immune cells that act like brakes to prevent the system from attacking healthy tissues. One of the primary immune cells is the T-cell, which circulates through the body to identify and destroy abnormal cells, including cancerous ones. T-cells have a checkpoint protein on their surface called Programmed Death-1 (PD-1), a receptor that helps suppress T-cell activity.
Some cancer cells exploit this braking system by producing a partner protein on their surface called Programmed Death-Ligand 1 (PD-L1). When PD-L1 on a cancer cell binds to the PD-1 receptor on a T-cell, it sends an “off” signal. This interaction prevents the T-cell from recognizing the cancer cell as a threat, allowing the cancer to hide and grow without being attacked by the immune system.
Anti-PD-1 drugs are a type of immunotherapy called checkpoint inhibitors that work by disrupting this interaction. These drugs are monoclonal antibodies, which are lab-created proteins designed to bind directly to the PD-1 receptor on the T-cell. By physically blocking the PD-1 receptor, the anti-PD-1 drug prevents PD-L1 on the cancer cell from connecting with it. This action is analogous to releasing the brakes on the immune system.
With the PD-1 receptor blocked, the “off” signal cannot be sent, and the T-cell is reactivated to recognize and attack cancer cells. This process restores the immune system’s natural ability to eliminate threats. This blockade can also lead to the creation of memory T-cells, which may contribute to a more durable and long-lasting anti-tumor response.
Cancers Treated and Common Drug Names
Anti-PD-1 therapies are approved for a growing list of malignancies. They are frequently used for advanced melanoma to shrink tumors and lower the risk of recurrence after surgery. Another major area of use is non-small cell lung cancer (NSCLC), especially for patients whose tumors express the PD-L1 protein. Other cancers where anti-PD-1 drugs are an established treatment include:
- Kidney cancer (renal cell carcinoma)
- Bladder cancer
- Head and neck cancers
- Classical Hodgkin lymphoma
The versatility of these drugs comes from their mechanism, which targets a process of immune evasion used by many cancers, not a specific tumor type. For this reason, they are also approved for any solid tumor with a specific genetic feature known as mismatch repair deficiency (dMMR), regardless of where the cancer originated. This “site-agnostic” approval means the treatment targets a biomarker rather than an anatomical location.
Several anti-PD-1 drugs are common in clinical practice. Pembrolizumab (Keytruda) and nivolumab (Opdivo) were among the first approved and are widely used for melanoma, NSCLC, and other cancers. Cemiplimab (Libtayo) is another prominent anti-PD-1 drug, approved for cutaneous squamous cell carcinoma, basal cell carcinoma, and certain types of NSCLC. These drugs are often used alone or combined with other treatments.
Understanding Immune-Related Side Effects
Anti-PD-1 drugs amplify the immune system’s activity, which can lead to it mistakenly attacking healthy organs and tissues. These side effects are known as immune-related adverse events (irAEs). Unlike side effects from chemotherapy, irAEs are a direct consequence of an activated immune system, not the drug’s toxicity. Any organ system in the body can be affected.
Common side effects often involve the skin, manifesting as a rash or itching, and the gastrointestinal tract, which can lead to diarrhea or colitis (inflammation of the colon). Fatigue is another frequently reported symptom. Other organs can be affected as well; for instance, inflammation of the lungs is known as pneumonitis, and inflammation of the liver is called hepatitis. The endocrine glands, which produce hormones, can also be targeted, leading to conditions like hypothyroidism.
While many of these side effects are mild to moderate and can be managed, some can be severe or life-threatening if not addressed promptly. Patient education is a key part of treatment, and patients are instructed to report any new or worsening symptoms to their healthcare team immediately. Early intervention, which often involves temporarily stopping the immunotherapy and administering corticosteroids to suppress the immune response, is used for managing these side effects safely.
What to Expect During Treatment
Treatment with anti-PD-1 drugs is administered in a clinical setting, such as a hospital outpatient department or an infusion center. The medication is delivered into the bloodstream through an intravenous (IV) infusion. This process involves inserting a small needle, connected to a tube, into a vein in the arm. The infusion itself is a quiet and straightforward procedure.
The duration of an infusion session can vary but often lasts between 30 and 90 minutes. The frequency of these treatments is determined by the specific drug being used and the treatment plan designed by the oncology team. A common schedule might involve receiving an infusion every two, three, four, or six weeks. This cyclical approach allows the body to recover between doses while maintaining a therapeutic level of the drug.
Throughout the course of treatment, patients undergo regular monitoring to assess the therapy’s effectiveness and to watch for side effects. This includes frequent check-ins with the medical team to discuss any symptoms. Periodic imaging tests, such as CT or PET scans, are used to measure the size of the tumors and determine how the cancer is responding to the treatment. This ongoing evaluation allows doctors to make informed decisions about continuing, pausing, or adjusting the therapy as needed.