Tumour Immunology Flashcards
What are the main differences between CD4+ and CD8+ T cells.
CD4+ are helper T cells. Activated by peptide + MHCII. Display CD40 ligands on surface and are either TH1 or TH2.
CD8+ = cytotoxic T cells. Activated by peptide + MHC Class I. Display FasL on surface.
Outline the roles of TH1 and TH2.
TH1 - display CD40 ligand. MACROPHAGES infected with intracellular bacteria - activated through cell-cell contact or through IFN-Y secretion.
TH2 - CD40 ligand. CD40 on a specific B-CELL infected with bacterial toxin. Activate EOSINOPHILS through cytokine release e.g. IL-4
what are Coley’s toxins?
In 1893 Coley observed spontaneous remission in cancer patients after injection with a mixture of killed infectious agents (IR mounted also directed against the tumour).
What are the main types of tumour specific antigens.
Novel fusion products - BCR/ABL in CML
Mutated oncogene or TS - p53 in head and neck SCC.
Exome sequencing - e.g. melanomas express high proportion of patient-specific NEO-ANTIGENS.
Onco-viral protein - EBV
What are the types of tumour associated antigens?
Aberrantly expressed normal genes - HER2
Overexpressed cell antigens - HER2
Differentiation antigens - tyrosinase
MAGE-1 expressed normally in germ cells.
Abnormal PTM - MUC1.
How can chronic inflammation promote tumourigenesis?
Initiation - generates genotoxic stress
Promotion - induces cell proliferation
Progression - enhances angiogenesis and tissue invasion.
What is the evidence linking cancer and inflammation?
Chronic inflammatory diseases increase cancer risk.
NSAID reduce risk of colon and breast cancers.
Signalling pathways involved in inflammation operate downstream of oncogenic mutations.
Inflammatory cells, chemokines & cytokines present in tumours from earliest stages but tumour still develops.
Target inflammatory mediators to decrease incidence and spread of cancers
How is TGF-B immunosuppressive?
May suppress CTL activation through SMAD activation and direct binding of SMAD/ATF1 complexes to granzyme B promoter regions.
Suppresses CTL activation by inducing Tregs.
How do tumour associated neutrophils affect tumourigenesis?
Antitumoural by secreting TGF-B
Promote genetic instability through ROS / RNS releasen
Release VEGF and MMP.
What evidence links Immune control of tumours?
Coley's toxins Mouse models of tumour rejection Enhanced susceptibility to chemical induced tumours. Immune suppressed patients High TILs = good outcome.
