Cardiac Complications in Immune Checkpoint Inhibition Therapy

Figures

• 

  Figure 1. Distinct roles of CTLA-4 and PD-1/PD-L1 in the regulation of antitumor immune responses. (A) Interactions between CTLA-4/B7 and PD-1/PD-L1 inhibit T cell-mediated tumor cell killing. (B) Blockade of CTLA-4, PD-1, and PD-L1 results in T cell activation and proliferation, which reactivates T cell-mediated tumor cell killing.

• 

  Figure 2. The clinical spectrum of irAEs associated with immune checkpoint inhibitors. irAEs, immune-related adverse events.

• 

  Figure 3. The role of immune checkpoints in establishing peripheral tolerance to the heart. During the establishment of central tolerance in the thymus, most autoreactive T cells are deleted; however, some autoreactive T cells are released into the periphery. In health, peripheral tolerance mechanisms keep these cells in check. CTLA-4 competes with CD28 to downregulate T-cell activation, resulting in immunotolerance and prevention of pathologic immune responses to cardiac-antigens. PD-1-PD-1 ligand interactions also maintain the cardiac-reactive T cells in an anergic state. Antibodies against CTLA-4, PD-1, or PD-L1 may activate cardiac antigen-reactive T cells that escape central tolerance. These T cells can clonally expand and attack the heart.