Pembrolizumab is a checkpoint inhibitor targeting PD-1 (programmed death-1). Its immune-mediated anti-tumour activity results from:

• A Direct induction of tumour cell apoptosis via DR5 receptor activation
• B Stimulating CD28 costimulatory pathway on naive T cells in lymph nodes
• C Blocking CTLA-4 on T-regulatory cells, reducing immune suppression in the tumour microenvironment
• D Blocking PD-1 on T cells, preventing PD-L1/PD-L2 on tumour cells from sending an inhibitory 'off' signal to effector T cells ✓

Explanation

Pembrolizumab is a humanised anti-PD-1 IgG4 monoclonal antibody that blocks the interaction between PD-1 on activated T cells and its ligands PD-L1/PD-L2 on tumour cells (and antigen-presenting cells). Normally, tumour cells exploit this pathway to 'turn off' infiltrating cytotoxic T cells; PD-1 blockade restores effector T-cell function. CTLA-4 blockade is the mechanism of ipilimumab; CD28 stimulation alone without CTLA-4/PD-1 context would not be the primary PD-1 inhibitor mechanism.

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

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Written and medically reviewed by the StethoPrep medical team.