Pembrolizumab (anti-PD-1) and ipilimumab (anti-CTLA-4) are checkpoint inhibitors. The distinct immune regulation site of each is:

• A Pembrolizumab acts in lymph nodes (priming phase); ipilimumab acts in tumor tissue (effector phase)
• B Pembrolizumab blocks PD-1 on T cells, restoring T-cell effector function in the tumor microenvironment (effector phase); ipilimumab blocks CTLA-4 on T cells in lymph nodes during antigen presentation (priming phase) ✓
• C Both act at the priming phase in lymph nodes, but ipilimumab blocks a weaker checkpoint
• D Pembrolizumab acts on regulatory T cells; ipilimumab acts on cytotoxic T cells

Explanation

CTLA-4 (targeted by ipilimumab) is expressed on T cells during the priming phase in lymph nodes; it competes with CD28 for B7 ligands on antigen-presenting cells, raising the activation threshold. Anti-CTLA-4 lowers this threshold, amplifying T-cell priming. PD-1 (targeted by pembrolizumab) is expressed on activated T cells infiltrating tumors; PD-L1 on tumor cells engages PD-1, exhausting T cells in the tumor microenvironment. Anti-PD-1 restores effector T-cell activity within the tumor. The sequential combination of both checkpoints provides synergistic antitumor activity.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.