Ipilimumab differs mechanistically from pembrolizumab because it blocks:

• A PD-L1 on tumour cells, preventing engagement of PD-1
• B LAG-3 on exhausted T cells
• C CTLA-4, permitting CD28-mediated costimulation during T cell priming ✓
• D CTLA-4 expressed selectively on tumour-infiltrating lymphocytes at the tumour site only

Explanation

CTLA-4 competes with CD28 for C7-1/C7-2 on antigen-presenting cells and delivers inhibitory signals during priming in lymph nodes. Ipilimumab removes this brake, enhancing costimulation, which also explains its higher rate of immune-related colitis, dermatitis and endocrinopathies compared with PD-1 inhibitors. Pembrolizumab blocks PD-1, a checkpoint operating mainly in the tumour microenvironment on previously activated T cells. CTLA-4 expression is broader than tumour tissue alone.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.