PD-L1 antibodies are a type of immunotherapy drug used to treat cancer by targeting the PD-L1 (programmed death-ligand 1) pathway, an essential checkpoint in the immune system. PD-L1, expressed on tumor cells and immune cells, binds to the PD-1 receptor on T cells, leading to immune suppression. Blocking this interaction enhances T cell activity against cancer cells.

Mechanism of Action

• PD-L1 antibodies block PD-L1 from binding to PD-1.
• This blockade prevents the inhibitory signal, thereby reactivating T cells to attack cancer cells.

Approved PD-L1 Antibodies

• Atezolizumab (Tecentriq): Used for NSCLC, urothelial carcinoma.
• Durvalumab (Imfinzi): Used for NSCLC, urothelial carcinoma.
• Avelumab (Bavencio): Used for Merkel cell carcinoma, urothelial carcinoma.

Clinical Applications

• PD-L1 antibodies are used as monotherapies or in combination with other treatments like chemotherapy, radiation, or other immune checkpoint inhibitors.
• They are effective in cancers with high PD-L1 expression or specific genetic alterations.

Adverse Effects

• Immune-related adverse events (irAEs) due to increased immune activation, similar to PD-1 antibodies:
  • Dermatologic: Rash, pruritus.
  • Gastrointestinal: Colitis, diarrhea.
  • Hepatic: Hepatitis.
  • Endocrine: Thyroid dysfunction, adrenal insufficiency.
  • Pulmonary: Pneumonitis.

Biomarkers for Response

• PD-L1 expression levels on tumor cells and immune cells.
• High PD-L1 expression correlates with better responses to PD-L1 blockade.

Resistance Mechanisms

• Primary resistance: Intrinsic tumor factors prevent initial response.
• Acquired resistance: Tumors adapt, leading to loss of response, often through upregulation of alternative immune checkpoints or loss of antigen presentation.

Future Directions

• Research on combination therapies to enhance efficacy and overcome resistance.
• Development of new biomarkers to better predict response.
• Exploration of PD-L1 antibodies in non-cancerous diseases, such as autoimmune disorders and chronic infections.