Category: immune_innate
T-cell activation requires antigen recognition (TCR-MHC) + co-stimulation (CD28-B7) but is balanced by inhibitory checkpoints — PD-1 (T-cell) engages PD-L1/PD-L2 (tumor or APC) → T-cell exhaustion. CTLA-4 outcompetes CD28 for B7 → blunts initial priming. Tumors hijack checkpoints to evade immunosurveillance. Checkpoint blockade releases the brake: anti-PD-1 (nivolumab, pembrolizumab) on T cells; anti-PD-L1 (atezolizumab, durvalumab) on tumors; anti-CTLA-4 (ipilimumab) priming-phase. Indications expanded to melanoma → NSCLC → renal → bladder → HCC → MSI-high tumors of any origin. Toxicity is autoimmune (irAEs): colitis, pneumonitis, hepatitis, endocrinopathies (thyroiditis → hypothyroidism, hypophysitis, T1DM, adrenal insufficiency) — managed by holding the drug ± systemic steroids.