Ipilimumab differs from nivolumab in both site of immune action and toxicity profile. Which pairing is correct?
- A Blocks CTLA-4 at the tumour interface, with pneumonitis as its characteristic adverse event
- B Blocks CTLA-4 during T cell priming in lymph nodes, with colitis as its characteristic immune-related adverse event ✓
- C Blocks PD-L1 on tumour cells, with thyroiditis as its dominant toxicity
- D Blocks LAG-3 on regulatory T cells, with hypophysitis as its dominant toxicity
Correct answer: B. Blocks CTLA-4 during T cell priming in lymph nodes, with colitis as its characteristic immune-related adverse event
Explanation
CTLA-4 competes with CD28 for A7 ligands early in T cell activation in lymphoid organs, so ipilimumab releases the brakes on priming and expands autoreactive clones, producing more frequent and severe colitis and hypophysitis than PD-1 agents. Nivolumab acts later, at the effector phase in peripheral tissue where PD-1 engages PD-L1. Anti-PD-1 therapy more typically causes pneumonitis. LAG-3 blockade refers to relatlimab, a different checkpoint molecule.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
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