Tumor antigens

1. Concept

The immune system both protects against and shapes tumors. Evidence: lymphocytic (mostly T-cell) infiltration correlates inversely with progression (more infiltration = less progression), and immunocompromised patients have higher cancer rates. Tumor antigens are antigens on tumors that can elicit a host immune response.

2. Two main categories

	Tumor-specific antigen (TSA)	Tumor-associated antigen (TAA)
Expression	Only on tumor cells	Tumor + some normal cells
Immune response	Strong	Weak (partial tolerance)
Examples	Mutated oncoproteins/neoantigens: BCR-ABL, RAS, p53; viral oncoproteins (HPV E6/E7)	Overexpressed/self proteins

• TSAs are more important for protection; TAAs are more useful for detection, monitoring, and immunotherapy targeting.

3. Types of tumor-associated antigens

• Overexpressed self-proteins — e.g. tyrosinase in melanoma; HER2/neu.
• Cancer-testis (oncospermatogonal) antigens — silent in adult tissue, expressed in sperm + tumor (sperm lacks MHC I).
• Oncofetal antigens — expressed in embryogenesis, re-expressed in tumors; serum markers (AFP, CEA).
• Viral antigens — HPV/HBV latency antigens (vaccination targets).
• Altered cell-surface glycoproteins — gangliosides (melanoma), MUC-1 (breast), blood-group antigens.
• Differentiation antigens — lineage markers identifying tissue of origin / therapy targets (e.g. CD20 → B-cell).

💡 High-yield: TSA (tumor-only, strong: mutated RAS/p53/BCR-ABL, viral E6/E7) → protection. TAA (tumor + normal, weak) → detection/therapy. TAA types: overexpressed (tyrosinase, HER2), cancer-testis (no MHC I in sperm), oncofetal (AFP, CEA — tumor markers), viral, glycoproteins (MUC-1), differentiation (CD20). Presented on MHC I → CD8+ CTL.