Lesson 12
Cancer Detection by Immune system
Tumour specific antigens (TSA) - found on tumour cells
Tumour associated antigens (TAA) - found on tumour and normal cells
Taken up by antigen presenting cells like dendritic cells and presented on their MHC Class II
Recognised by CD4+ T helper cells, which are activated to release cytokines
Cancer Destruction by Immune System
B cells become antibody producing plasma cells
CD8+ T cells activated by cytokines and bind to antigens via MHC class I to destroy tumour cells
Antibodies
bind to antigens on tumour cells, signalling Natural Killer cells to attack
trigger opsonization, neutralization and activation of complement system
Immunoevasion
Repression of Antigen presentation
by reducing expression of MHC I on surface
by reducing antigen processing
Repression of natural killer cell ligands (Rae 1) that bind to the NKG2D on NK cells
Induced Immunocyte Apoptosis
Tumour cells produce Fas ligand that binds to Fas receptors on T cells to induce apoptosis
Inactivate Immune cells
Treg cells and cancer cells release immunosuppressive cytokines to inhibit activation of naïve T cells
Tregs express CTLA-4 on their surface, which downregulate B7 (CD80) expression by antigen presenting cells (APC), depriving co-stimulatory signal to responder T cells.
Immunotherapy
"Naked" monoclonal antibodies
block specific target on cancer cell or on areas surrounding cancer cells and activate immune system
Antibody-Drug Conjugate
antibodies conjugated with anti-cancer drugs bind to cancer cell, delivering a toxic that can kill them
Bispecific antibodies (T cell engagers)
bring T cells close to cancer cell, enabling them to eliminate the cells