T-cells Patrol for Tumor Antigens
Placeholder: T-cells constantly scan tissue for abnormal cells.
- ~10^7: T-cell receptor diversity (placeholder stat)
- Neoantigens: Tumor antigen types (placeholder stat)
- Minutes: Immune synapse time (placeholder stat)
- Variable: Baseline kill rate (placeholder stat)
Antigen recognition basics
Placeholder text: TCR engages MHC-presented tumor peptide.
Normal T-cell activation
Placeholder text: costimulation drives cytotoxic program.
Tumors Express PD-L1 to Hide
Placeholder: tumor cells upregulate PD-L1 under immune pressure.
- Common: PD-L1+ tumors (placeholder stat)
- IFN-γ: Induction driver (placeholder stat)
- CD274: PD-L1 gene (placeholder stat)
- IHC: Expression assay (placeholder stat)
Why tumors express PD-L1
Placeholder text: adaptive immune resistance mechanism.
Interferon feedback loop
Placeholder text: T-cell attack itself induces PD-L1.
PD-1/PD-L1 Delivers the Brake Signal
Placeholder: checkpoint engagement shuts down T-cell attack.
- CD279: PD-1 receptor (placeholder stat)
- Inhibitory: Signal type (placeholder stat)
- SHP-2: Downstream effect (placeholder stat)
- Self-tolerance: Normal role (placeholder stat)
Checkpoint signaling
Placeholder text: ITSM/ITIM motifs recruit phosphatases.
Hijacking self-tolerance
Placeholder text: tumor exploits a normal safety brake.
Placeholder highlight: PD-1 normally prevents autoimmunity.
Pembrolizumab Blocks PD-1
Placeholder: monoclonal antibody physically blocks the receptor.
- Anti-PD-1 mAb: Drug class (placeholder stat)
- PD-1 (CD279): Target (placeholder stat)
- 2014: Approval year (placeholder stat)
- IV infusion: Administration (placeholder stat)
Mechanism of blockade
Placeholder text: antibody outcompetes PD-L1 for PD-1.
Dose-response relationship
Placeholder text: higher dose increases receptor occupancy.
Restored T-cell Attack and Tumor Killing
Placeholder: brake removed, T-cell resumes cytotoxic function.
- Subset: Durable response rate (placeholder stat)
- Present: irAE risk (placeholder stat)
- PD-L1 CPS: Response marker (placeholder stat)
- Chemo/other: Combination use (placeholder stat)
Cytotoxic killing restored
Placeholder text: granzyme/perforin release resumes.
Risks of releasing the brake
Placeholder text: reduced braking can cause autoimmune-like effects.
Placeholder highlight: durable responses possible, side effects too.