Ipilimumab differs mechanistically from pembrolizumab in its site of checkpoint blockade. Ipilimumab acts by:

• A Agonising CD28 to provide a stronger costimulatory signal than B7-1
• B Blocking CTLA-4 at the effector phase within tumour tissue
• C Blocking PD-L1 on tumour cells to prevent T-cell anergy
• D Blocking CTLA-4, thereby releasing inhibition at the T-cell priming stage in lymph nodes ✓

Explanation

CTLA-4 competes with CD28 for B7 (CD80/CD86) on antigen-presenting cells and delivers an inhibitory signal during naive T-cell activation in lymph nodes. Ipilimumab blocks CTLA-4, permitting costimulation and expansion of antitumour T-cell clones. PD-1/PD-L1 agents act later, at the effector phase in peripheral tissues and tumours. Ipilimumab antagonises rather than agonises the pathway, so option A misstates the pharmacology.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.