Tumor immunity and immune surveillance

1. Concept

Immune surveillance = the immune system continuously detects and eliminates transformed cells. Proof: cancers are more frequent in immunocompromised hosts. Yet most cancers arise in immunocompetent people because tumors escape surveillance.

2. Anti-tumor effector mechanisms

Cell-mediated immunity dominates.

Effector	Action
CD8+ cytotoxic T cells	Recognize tumor antigen on MHC I → kill; key against viral oncogenesis
NK cells	First line, no prior sensitization; kill cells that downregulate MHC I; activated by stress-induced ligands on damaged/tumor cells
Macrophages	Activated by IFN-γ (from T/NK cells) → ROS + TNF → tumor killing

Note the complementarity: CTLs need MHC I, NK cells attack when MHC I is lost — so tumors can’t escape both by the same trick.

3. Tumor escape mechanisms

1. Selective outgrowth of antigen-negative variants — immunogenic subclones eliminated, leaving non-immunogenic cells (immunoediting).
2. Loss/reduced MHC I — escape CTLs (but still NK-susceptible).
3. Immunosuppression — secrete TGF-β/TNF-β; recruit/activate regulatory T cells (Treg).
4. Antigen masking — thick glycocalyx (mucopolysaccharides) blocks immune access.
5. Killing CTLs — tumor FasL binds Fas on T cells → T-cell apoptosis.

4. Therapeutic relevance

• Checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) reverses tumor-induced T-cell exhaustion and restores anti-tumor immunity.

💡 High-yield: Effectors: CD8+ CTL (MHC I-restricted), NK (kill MHC I-low), macrophages (IFN-γ → ROS/TNF). Escape: antigen-negative variants, MHC I loss, immunosuppression (TGF-β, Treg), antigen masking, FasL killing of T cells. Therapy = checkpoint inhibitors (PD-1/PD-L1, CTLA-4).