U01.04.024 Immune checkpoint interactions

Immune checkpoint interactions are crucial signals that modulate T cell activation and function, influencing the immune response against tumor cells. These interactions are targeted by several cancer immunotherapies to enhance the immune system’s ability to fight cancer.

Key Interactions and Immunotherapies

PD-1 and PD-L1/2 Interaction
- Mechanism: PD-1 on T cells interacts with PD-L1/2 on tumor cells or immune cells within the tumor microenvironment, leading to T cell dysfunction or exhaustion.
- Immunotherapy:
  - Anti-PD-1 antibodies: Pembrolizumab, Nivolumab
  - Anti-PD-L1 antibodies: Atezolizumab, Durvalumab, Avelumab
CTLA-4 and CD28 Interaction
- Mechanism: CTLA-4 on T cells competes with CD28 for binding to B7 on antigen-presenting cells (APCs), resulting in a loss of T cell costimulatory signals.
- Immunotherapy:
  - Anti-CTLA-4 antibody: Ipilimumab

Table: Key Components and Therapies

Component	Description
PD-1	Receptor on T cells
PD-L1/2	Ligands on tumor or immune cells in the tumor microenvironment
CTLA-4	Receptor on T cells that inhibits activation
CD28	Co-stimulatory receptor on T cells
B7	Ligand on APCs that binds to CD28 or CTLA-4
MHC I	Major histocompatibility complex class I, presents antigen to TCR
TCR	T cell receptor, recognizes antigen presented by MHC I

Table: Key Components and Therapies

Immunotherapies

Drug	Target	Type
Pembrolizumab	PD-1	Anti-PD-1 antibody
Nivolumab	PD-1	Anti-PD-1 antibody
Atezolizumab	PD-L1	Anti-PD-L1 antibody
Durvalumab	PD-L1	Anti-PD-L1 antibody
Avelumab	PD-L1	Anti-PD-L1 antibody
Ipilimumab	CTLA-4	Anti-CTLA-4 antibody

Immunotherapies

Points to Remember

PD-1/PD-L1 Interaction: Critical in T cell exhaustion; targeted by anti-PD-1 and anti-PD-L1 therapies.
CTLA-4/CD28 Interaction: Regulates T cell activation; targeted by anti-CTLA-4 therapy.
Efficacy of Therapies: The effectiveness of immunotherapies can vary based on the specific checkpoint targeted and the tumor microenvironment.

USMLE Step 1 Review Series

Curriculum

U01.04.024 Immune checkpoint interactions

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