The Role of the Immune System in Cancer Flashcards
What is the normal immune surveillance in cancer?
- tumour cells initiate release of antigens
- = release of danger cytokines (INF-alpha and heat shock proteins)
- activation and maturation of dendritic cells to present tumour antigens to CD8 and CD4 cells
- subsequent T-cytotoxic destruction of the tumour
How do cancers evade the immune systems?
- tumour antigens immunogenic
- self antigens = potential tolerance
- evolved mechanisms which prevent immune rejection
What are the evolved mechanisms of cancer cells
- secrete inhibitory cytokines
- create unique microenvironment
- alter host immune system locally and systemically
- induce inhibitory T cell subsets
What is cancer immunoediting?
- functional cancer immunosurveillance processes and suppresses tumour growth
- dual role of immune system in interaction between host and tumour
What are the 3 characteristics of immunoediting?
- elimation of cancer cells by immune system
- equilibrium between cancer cells and immune system
- escape of cancer cells from immune system
How do tumours escape by natural selection?
- genomic instability of cells = natural selection of tumour variants = effective immunotherapy
What is the significance of increase T regulatory cells in cancer?
- suppressor T cells
- CD4+ T cells
- regulate immune response through antigen specific suppression of effector CD4+ and CD8+ T cells
- amount of T regs predict survival
- T cells in cancer exhausted due to chronic stimulation by cancer
- PD1 important marker increased on cell surface
What is cancer immunology?
- study of how cancer affects host immune system
What is passive cancer immunology?
administration of agent
- monoclonal antibodies
- transfer of effector cells
How are monoclonal antibodies produced?
- by single type of cell
- specific for an antigen
- inject human cancer cells into mice and mouse makes antibodies with are fused in lab = hybridoma
- hybridoma produces large quantities of antibodies
- mouse proteins chimeric or humanised
What are the different approaches of monoclonal antibody treatment?
- unconjugated (complement mediated lysis)
- coupled to toxins (immunotoxins)
- coupled to radioisoptopes (radioummunoconjugates)
How are monoclonal antibodies humanised?
- otherwise patients develop anti-mouse antibodies
- develop recombinant molecules which maintain antigen binding of murine MoABs coupled to human Ig backbone
What are the ideal targets for MoAb therapy?
- expressed on all tumour cells
- high copy number
- no mutations/variant antigens
- required for critical biologic function/cell survival
- not shed/secreted
- not modulated after antibody binding
How do MoAbs work?
- antibody dependent cell mediated cytotoxicity
- complement dependent cytotoxicity
- apoptosis
How does antibody-dependent cell mediated cytotoxicity work?
- Fc region on phagocytic cells (NK cells, macrophages, neutrophils)
- effector cells release mediators which damage and destroy malignant B cells
- malignant B cells phagocytosed
