ImmuncheckpointTherapien

Immune checkpoints are regulatory pathways in the immune system that help maintain self-tolerance and prevent autoimmunity by dampening T-cell activity. Cancer cells can exploit these checkpoints to evade immune attack. The best characterized checkpoints are CTLA-4 and the PD-1/PD-L1 axis, which act at different stages of T-cell activation and effector function.

Immune checkpoint inhibitors are monoclonal antibodies or fusion proteins that block checkpoint proteins, thereby reactivating T cells to attack tumors. Examples include anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab), and anti-PD-L1 (atezolizumab, durvalumab).

They are approved for numerous cancers, often in advanced or previously treated disease, and some indications include combinations (e.g., nivolumab plus ipilimumab). Response rates vary; durable responses can occur even after therapy ends. Biomarkers such as PD-L1 expression, tumor mutational burden, and microsatellite instability status help guide use in certain contexts, but they are not perfect predictors.

Common adverse events are immune-related, reflecting heightened immune activity in normal tissues. These include rash, colitis, pneumonitis, hepatitis, endocrinopathies, and rare but serious events. Management depends on severity and may involve treatment interruption and systemic corticosteroids or other immunosuppressants. Early recognition is important; some irAEs require long-term care.

Limitations include primary resistance, acquired resistance, and high cost. Not all patients benefit, and real-world outcomes depend on tumor type, patient health, and biomarkers. Ongoing research explores additional checkpoints such as LAG-3, TIM-3, and TIGIT, as well as combinations with chemotherapy, targeted therapies, or vaccines.