Endometrial cancer originates in the lining of the uterus, known as the endometrium. It is the most common gynecological malignancy in developed nations. While early detection often leads to effective treatment, advanced or recurrent cases present significant challenges. Immunotherapy is a treatment approach that harnesses the body’s own defense mechanisms to combat cancer. This innovative therapy aims to bolster the immune system’s natural ability to recognize and eliminate cancer cells.
Understanding Immunotherapy
The body’s immune system typically identifies and destroys abnormal cells, including those that could become cancerous. This intricate system relies on immune cells, such as T cells, to scan for specific markers on cell surfaces. Cancer cells, however, can develop mechanisms to evade this detection. They might produce signals that tell immune cells to “turn off,” allowing them to grow unchecked.
Immunotherapy works by “unmasking” these cancer cells or by boosting the immune system’s ability to fight them. Unlike chemotherapy, which directly attacks rapidly dividing cells, or radiation, which uses high-energy rays to destroy cancer cells, immunotherapy specifically targets the interactions between cancer cells and immune cells. By disrupting the signals that allow cancer to hide, immunotherapy aims to reactivate the body’s natural defenses. This approach helps the immune system better recognize cancer cells as foreign invaders.
Immunotherapy’s Role in Endometrial Cancer
Immunotherapy is increasingly applied to endometrial cancer, particularly in advanced or recurrent cases where traditional treatments may be less effective. A primary class of immunotherapy drugs used for endometrial cancer are immune checkpoint inhibitors. These drugs target specific proteins on immune cells or cancer cells that act as “checkpoints” to regulate the immune response.
One common pathway targeted is the PD-1/PD-L1 pathway. PD-1 and PD-L1 are proteins found on immune cells (like T cells) and cancer cells, respectively. When PD-1 on T cells binds to PD-L1 on cancer cells, it sends a signal that tells the T cell to switch off, preventing it from attacking the tumor.
Immune checkpoint inhibitors, such as pembrolizumab, dostarlimab, nivolumab, durvalumab, and avelumab, work by blocking this interaction. By preventing PD-1 and PD-L1 from binding, these drugs release the “brakes” on the T cells, allowing them to remain active and recognize and destroy cancer cells. This mechanism helps to boost the immune response.
Determining Eligibility for Immunotherapy
Patient eligibility for immunotherapy in endometrial cancer often depends on specific characteristics of the tumor. Biomarkers play a significant role in guiding these treatment decisions. A key factor is the tumor’s microsatellite instability (MSI-H) status or mismatch repair deficiency (dMMR). These genetic characteristics indicate a high number of mutations within the cancer cells, which can make them more recognizable to the immune system.
Approximately 20-30% of endometrial cancers exhibit dMMR or MSI-H. Tumors with these features tend to have a higher tumor mutational burden (TMB), leading to the production of more abnormal proteins that the immune system can identify as foreign. Testing for MSI-H or dMMR is commonly performed using immunohistochemistry or next-generation sequencing. Other considerations for eligibility include the cancer stage, prior treatments received, and the patient’s overall health status.
Navigating Immunotherapy’s Effects
Immunotherapy can cause unique side effects, distinct from those associated with chemotherapy. These are often referred to as immune-related adverse events (irAEs) because they result from the immune system becoming overactive and attacking healthy tissues.
Common irAEs include fatigue, skin rashes, itching, and thyroiditis. Some individuals may also experience gastrointestinal issues like diarrhea or colitis, joint pain, muscle aches, or pneumonitis (inflammation of the lungs). While some side effects may be mild, others can be more serious, affecting organs like the liver (hepatotoxicity) or causing hematologic toxicities. Careful monitoring is important, and patients are encouraged to report any new or worsening symptoms promptly. Management often involves corticosteroids to suppress the immune system if irAEs become severe.