Immunotherapy represents a shift in cancer treatment by harnessing the body’s own defense mechanisms to fight the disease. Unlike chemotherapy, which directly attacks fast-growing cells, this approach uses specialized medications to enhance the immune system’s ability to recognize and destroy cancer cells. For individuals with lung cancer, particularly non-small cell lung cancer (NSCLC), immunotherapy has become a standard part of the treatment landscape. This strategy involves mobilizing immune cells, such as T-cells, that are equipped to eliminate abnormal cells, offering a highly specific way to manage the disease.
How Immunotherapy Works Against Lung Cancer
The immune system has built-in mechanisms, known as checkpoints, that act as “brakes” to prevent immune cells from mistakenly attacking healthy tissues. Cancer cells exploit these checkpoints by displaying certain proteins on their surface, sending a signal to T-cells to stand down. This process allows the tumor to evade detection and grow unchecked.
One of the most well-known checkpoint interactions involves a protein on the T-cell called Programmed Death-1 (PD-1) and its partner, Programmed Death-Ligand 1 (PD-L1), often found on the surface of lung cancer cells. When PD-1 binds to PD-L1, the T-cell receives an inhibitory signal, leading to its deactivation. This binding shields the cancer cell from immune destruction.
Immunotherapy drugs designed as immune checkpoint inhibitors work by blocking this specific PD-1/PD-L1 pathway. By disrupting the connection between the two proteins, the drugs release the “brakes” on the T-cells. This action re-activates the T-cells, allowing them to recognize the lung cancer cell as foreign and mount a targeted response against the tumor. The result is a restored ability for the immune system to control or shrink the cancer.
Key Types of Immunotherapy Drugs
The most widely used class of immunotherapy drugs for lung cancer are the Immune Checkpoint Inhibitors (ICIs). These agents are monoclonal antibodies, which are laboratory-made proteins designed to target and block specific checkpoint proteins.
PD-1 inhibitors block the PD-1 receptor on the surface of immune T-cells; examples include nivolumab and pembrolizumab. PD-L1 inhibitors block the PD-L1 protein found on the surface of the cancer cells; examples include atezolizumab and durvalumab.
A less common class of drugs are the Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) inhibitors, such as ipilimumab. CTLA-4 is another checkpoint protein that acts earlier in the immune response, regulating the initial activation of T-cells. CTLA-4 inhibitors are not typically used alone for lung cancer, but are sometimes combined with a PD-1 inhibitor to create a dual checkpoint blockade.
When Immunotherapy is Used in Treatment
Immunotherapy is a standard treatment for both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC). Its application varies depending on the cancer type and the stage of the disease. For advanced or metastatic NSCLC, an immune checkpoint inhibitor is often used as the initial treatment, either alone or combined with chemotherapy.
In earlier stages of NSCLC, immunotherapy is incorporated into the curative treatment plan. It can be given before surgery (neoadjuvant therapy) or after surgery and chemotherapy (adjuvant therapy) to reduce the risk of recurrence. For patients with locally advanced NSCLC that cannot be removed by surgery, immunotherapy is sometimes administered following chemoradiation.
For SCLC, immunotherapy is primarily used for extensive-stage disease. PD-L1 inhibitors are typically combined with platinum-based chemotherapy as a first-line treatment. Immunotherapy drugs are administered through an intravenous (IV) infusion, with cycles usually occurring every few weeks.
Understanding Immune-Related Side Effects
The side effects of immunotherapy are different from those caused by chemotherapy. These reactions are called immune-related adverse events (irAEs) and occur because the newly activated immune system can mistakenly target healthy organs. This off-target attack is an autoimmune reaction and can affect almost any organ system.
The most frequently reported irAEs involve the skin (rash) or the endocrine system (thyroid dysfunction). More serious, though less common, irAEs include inflammation of the lungs (pneumonitis) or inflammation of the colon (colitis). Management often involves corticosteroids, which are powerful anti-inflammatory medications that suppress the immune system. Immediate reporting of any new symptoms to the oncology team is important for quick diagnosis and effective management.