atezolizumab

Atezolizumab is an immune checkpoint inhibitor that targets programmed death-ligand 1 (PD-L1), which is expressed on tumor cells and tumor-infiltrating immune cells. Normally, PD-L1 binding to PD-1 on T cells delivers an inhibitory signal that suppresses T-cell activation, allowing tumor cells to evade immune destruction. By blocking PD-L1, atezolizumab restores T-cell-mediated antitumor immunity, allowing cytotoxic T cells to recognize and destroy cancer cells more effectively. It is FDA-approved for multiple malignancies, including non-small cell lung cancer (NSCLC), small cell lung cancer, urothelial carcinoma, hepatocellular carcinoma (often combined with bevacizumab), and triple-negative breast cancer (in combination with chemotherapy). Because it releases the brakes on the immune system, atezolizumab and other checkpoint inhibitors carry a distinct risk profile of immune-related adverse events (irAEs), including pneumonitis, colitis, hepatitis, endocrinopathies (thyroiditis, adrenal insufficiency, hypophysitis), dermatitis, and rarely myocarditis. Management of severe irAEs typically involves corticosteroids and discontinuation of therapy. For boards, it's important to distinguish PD-L1 inhibitors (atezolizumab, durvalumab, avelumab) from PD-1 inhibitors (nivolumab, pembrolizumab) and CTLA-4 inhibitors (ipilimumab), as they all modulate different steps of the immune checkpoint pathway but share overlapping toxicity profiles. Testing for PD-L1 expression via immunohistochemistry can help predict response in certain cancers, although response can occur even with low PD-L1 expression in some tumor types.