Esophageal cancer, a malignancy originating in the tube connecting the throat to the stomach, presents treatment challenges. Immunotherapy offers a different approach by harnessing the body’s own immune system to target and fight cancer cells. This method can provide lasting responses in certain patients.
How Immunotherapy Works
The immune system continuously surveys the body, identifying and eliminating foreign invaders and abnormal cells, including cancerous ones. Immune cells, particularly T lymphocytes or T cells, are equipped to recognize and destroy these threats. T cells have surface proteins, known as immune checkpoints, which regulate their activity to prevent excessive immune responses that could harm healthy tissues.
Cancer cells, however, can exploit these natural regulatory mechanisms to evade detection and destruction by the immune system. They achieve this by expressing certain proteins that interact with immune checkpoints, sending “off” signals to T cells. This interaction prevents T cells from recognizing the cancer cells as a threat and launching an attack. This is referred to as immune evasion. Tumors can restrict the recognition of antigens, inhibit the immune system directly, or induce T cell exhaustion, allowing them to grow unchecked.
Immunotherapy drugs, immune checkpoint inhibitors, are designed to block these “off” signals. By interrupting the binding between checkpoint proteins on immune cells and their partner proteins on cancer cells, these inhibitors “release the brakes” on the immune response. This allows the T cells to reactivate, recognize the cancer cells, and mount an attack against the tumor.
Immunotherapy Approaches for Esophageal Cancer
For esophageal cancer, immunotherapy primarily involves immune checkpoint inhibitors, particularly those targeting the PD-1/PD-L1 pathway. The programmed cell death protein 1 (PD-1) is a receptor on activated T cells, while its ligand, programmed death-ligand 1 (PD-L1), can be expressed on cancer cells. This interaction normally helps regulate the immune response, preventing the immune system from attacking healthy tissues.
Cancer cells often overexpress PD-L1, which binds to PD-1 on T cells, deactivating them and preventing an anti-tumor immune response. By blocking this PD-1/PD-L1 interaction, immunotherapy drugs, such as pembrolizumab or nivolumab, prevent the “off” signal from being sent to T cells. This enables the T cells to remain active, identifying and destroying esophageal cancer cells.
These inhibitors restore the T cells’ ability to recognize and target the cancer. The goal is to normalize the immune system’s function against the tumor rather than simply boosting immune cell activity. This targeted intervention addresses a mechanism by which esophageal cancer cells evade immune surveillance.
When Immunotherapy is Considered
Immunotherapy is considered for esophageal cancer in various clinical situations, depending on the disease stage. It is frequently used in advanced or metastatic esophageal cancer, where the disease has spread to distant parts of the body. In these cases, immunotherapy can be administered alone or in combination with chemotherapy, aiming to improve patient outcomes.
Immunotherapy can also be part of treatment plans in earlier stages, sometimes before or after surgery (neoadjuvant or adjuvant settings). The decision to use immunotherapy considers specific characteristics of the tumor, such as the expression level of PD-L1 on the cancer cells. Higher PD-L1 expression can indicate a greater likelihood of response to PD-1/PD-L1 inhibitors.
Patient eligibility for immunotherapy also involves an assessment of their overall health and other existing medical conditions. The specific type of esophageal cancer, such as adenocarcinoma or squamous cell carcinoma, can also influence treatment decisions. These factors guide oncologists in determining the most appropriate treatment strategy.
Managing Treatment and Potential Effects
Patients undergoing immunotherapy for esophageal cancer receive the treatment intravenously, often at regular intervals, such as every two to four weeks. The duration of treatment varies based on the patient’s response and tolerance, potentially continuing for several months or even longer. Close monitoring by the medical team is performed to assess treatment effectiveness and manage any emerging issues.
Immunotherapy can lead to side effects, which are termed immune-related adverse events (irAEs), because they result from the activated immune system affecting healthy tissues. Common irAEs can include fatigue, skin rashes, or itching. More serious but less frequent effects can involve inflammation of various organs, such as the colon (colitis), lungs (pneumonitis), liver (hepatitis), or endocrine glands like the thyroid.
These effects are monitored through regular blood tests and clinical evaluations. Management strategies for irAEs involve corticosteroids to reduce inflammation, and in some cases, temporary interruption or discontinuation of immunotherapy may be necessary. Prompt reporting of any new or worsening symptoms to the healthcare team is important for effective management.