Immunotherapy has emerged as an important approach in the treatment of cancer, particularly for kidney cancer. This treatment method harnesses the body’s own immune system to identify and attack cancer cells. Unlike traditional chemotherapy, which directly kills cancer cells, immunotherapy works by boosting, focusing, or restoring the immune system’s natural defenses. It has advanced the management of various cancers, including advanced or metastatic kidney cancer.
How Immunotherapy Works Against Kidney Cancer
The immune system protects the body by distinguishing between healthy cells and harmful invaders. A key component of this defense involves T cells, a type of white blood cell. These T cells have specific proteins on their surface, known as “checkpoint” proteins, which regulate immune responses, preventing them from becoming overactive and damaging healthy tissues.
Cancer cells, however, can exploit these checkpoints by producing partner proteins that bind to the T cells’ checkpoint proteins, effectively turning off the immune response. This interaction prevents the T cells from recognizing and attacking the cancer, allowing the tumor to evade destruction. Immunotherapy drugs are designed to block this interaction.
By blocking these checkpoint proteins, immunotherapy “releases the brakes” on the immune system. This allows T cells to become active again, enabling them to identify and target kidney cancer cells more effectively. Common checkpoint proteins targeted by these therapies include PD-1 (Programmed Death-1), PD-L1 (Programmed Death-Ligand 1), and CTLA-4 (Cytotoxic T-Lymphocyte-Associated protein 4).
Specific Immunotherapy Approaches for Kidney Cancer
Immune checkpoint inhibitors are a primary class of immunotherapy drugs used for kidney cancer. Nivolumab and pembrolizumab are examples of drugs that target the PD-1 protein on T cells. By blocking PD-1, these medications enhance the immune response against kidney cancer cells, leading to tumor shrinkage or slowed growth.
Avelumab is another type of immune checkpoint inhibitor that targets PD-L1, a protein often found on cancer cells and immune cells that binds to PD-1. Blocking PD-L1 also enhances the immune system’s ability to fight cancer. These PD-1 and PD-L1 inhibitors are often used as part of the initial treatment for advanced kidney cancer, sometimes in combination with other drugs.
Ipilimumab is a different type of immune checkpoint inhibitor that blocks CTLA-4, another checkpoint protein on T cells. This drug is not typically used alone for kidney cancer but is often combined with nivolumab. This combination therapy further enhances the immune system’s ability to attack cancer cells.
While immune checkpoint inhibitors are the predominant immunotherapy for kidney cancer, cytokine therapy, which uses man-made versions of proteins like interleukin-2 (IL-2), has also been used in specific cases. These proteins boost the immune system to shrink cancer cells. However, cytokines are less commonly used now due to newer, more effective immune checkpoint inhibitors and their potential for serious side effects.
Patient Selection and Treatment Experience
Eligibility for immunotherapy in kidney cancer considers cancer stage, previous treatments, and overall health. Immunotherapy is most commonly used for advanced or metastatic kidney cancer, often for stage 3 or 4 disease. It can also be given as adjuvant therapy after surgery to lower the risk of recurrence.
Immunotherapy drugs are typically administered intravenously. The frequency of these infusions varies depending on the specific drug and combination, often ranging from once every two weeks to once every six weeks. The treatment continues until disease progression or if unacceptable side effects occur.
Patients undergoing immunotherapy may experience distinct side effects, known as immune-related adverse events (irAEs), due to immune system activation. Common irAEs can include fatigue, skin rashes, itching, diarrhea, and joint pain. More serious but less common side effects can involve inflammation in organs such as the liver, lungs, or thyroid gland.
The management of these side effects depends on their severity. Mild irAEs (Grade 1-2) might only require symptomatic treatments, while more severe reactions (Grade 3 or higher) often necessitate steroid treatment to reduce inflammation. Patients are closely monitored, and education about potential irAEs is provided to ensure early detection and proper management.