Question

Describe cancer immunotherapy and its predictive markers.

Hint:

Cancer immunotherapy, combined with predictive markers like PD-L1 expression and TMB, allows for more personalized treatment plans and can lead to significant improvements in patient outcomes.

Answer 1

Cancer immunotherapy is a treatment that uses the body's immune system to fight cancer. It has revolutionized cancer treatment by harnessing immune checkpoint inhibitors, cancer vaccines, and monoclonal antibodies to target cancer cells.
Step 1: Types of Cancer Immunotherapy:
1. Immune Checkpoint Inhibitors: These drugs block checkpoint proteins, such as PD-1, PD-L1, and CTLA-4, that prevent immune cells from attacking cancer cells. Common examples include pembrolizumab (Keytruda) and nivolumab (Opdivo), which are used in cancers like melanoma, lung cancer, and kidney cancer.
2. Monoclonal Antibodies: These are antibodies designed to target specific antigens on cancer cells. For example, trastuzumab (Herceptin) targets HER2-positive breast cancer cells.
3. Cancer Vaccines: Vaccines like the HPV vaccine (Cervarix, Gardasil) help prevent cancers caused by viral infections, while therapeutic vaccines like BCG (used in bladder cancer) stimulate the immune system to attack cancer cells.
Step 2: Predictive Markers in Immunotherapy:
1. PD-L1 Expression: The expression of PD-L1 on tumor cells or immune cells is a key predictive marker for response to immune checkpoint inhibitors. Tumors with high PD-L1 expression are more likely to respond to drugs like pembrolizumab and nivolumab.
2. Tumor Mutational Burden (TMB): TMB refers to the number of mutations in a tumor's DNA. A higher TMB is associated with a better response to immunotherapy, as it leads to the production of more neoantigens that the immune system can target.
3. Microsatellite Instability (MSI): MSI-high tumors, often found in colorectal and endometrial cancers, are more likely to respond to immune checkpoint inhibitors, making MSI a useful marker in predicting treatment efficacy.
4. CTLA-4 Expression: High expression of CTLA-4 can indicate a poor response to immunotherapy, but blocking this checkpoint with drugs like ipilimumab can improve treatment outcomes.
Step 3: Mechanism of Action:
Immunotherapy works by stimulating the immune system to recognize and destroy cancer cells. It can also prevent tumors from evading immune surveillance by blocking inhibitory signals that normally suppress immune responses.
Step 4: Side Effects:
Although effective, immunotherapy can cause immune-related adverse events, including inflammation of healthy tissues (e.g., colitis, hepatitis, pneumonitis). These side effects require careful monitoring and management.