checkpoint inhibitor therapy

Indications

• treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, bladder cancer, Hodgkin lymphoma, & colon cancers caused by DNA mismatch-repair deficiency

Adverse effects

• may increase risk of autoimmunne disease
• increased risk of endocrinopathy
  • thyroid disease: hypothyroidism, thyroiditis
  • adrenal disorders
  • hypophysitis
    • central adrenal insufficiency
    • secondary (central) hypothyroidism
  • type 1 diabetes
  • most mild, but may be serious

Procedure

• checkpoint inhibitors include:
  • ipilimumab (Yervoy) inhibits CTLA-4
  • pembrolizumab (Keytruda) inhibits PD-1
  • nivolumab (Opdivo) inhibits PD-1

Mechanism of action

• when T cells are activated, the activated T cells paradoxically produce 'checkpoint' proteins that then abort the T-cell attack
  • 2 checkpoint proteins are CTLA-4 & PD-1
• checkpoint inhibitor facilitate an uninhibited T-cell response to tumor antigens

Comparative biology

• in a mouse model for colon cancer, Bifidobacterium (B. pseudolongum) enhances effectiveness of checkpoint inhibitor therapy via production of inosine
  • this results in a more permeable gut-blood barrier increasing blood inosine concentrations, leading to systemic activation of antitumor T cells
  • Bifidobacterium species are increased in humans with colon cancer responding to checkpoint inhibitor therapy

More general terms

• cancer immunotherapy

Additional terms

• checkpoint inhibitor; immune checkpoint inhibitor; PD-1/PD-L1 inhibitor