Tumour immunology Flashcards
What is the etiology of cancer?
- Transformation of germline cells: inheritable cancers (<10%, Rb, BRCA1, 2)
- Transformation of somatic cells: noninheritable cancers (>90%)
- Environmental factors: UV (skin cancer), chemicals (lung cancer), pathogens (HPV causes cervical cancer, helicobacter causes stomach cancer)
What are the hallmarks of cancer?
- Growth self-sufficiency
- Evade apoptosis
- Ignore anti-proliferative signals
- Limitless replication potential
- Sustained angiogenesis
- Invade tissues
- Escape immune surveillance
What is the goal of tumour immunology?
to induce clinically effective anti‐tumour immune responses that would discriminate between tumour cells and normal cells in cancer patients
What is cancer immunosurveillance?
Immune system can recognize and destroy nascent transformed cells, normal control
What is cancer immunoediting?
- Tumours tend to be genetically unstable
- Immune system can kill and also induce changes in the tumour resulting in tumour escape and recurrence
- Allows tumours to be undetected
What are the 2 tumour antigens?
- Tumour Specific Antigens (TSA)
- Tumour Associated Antigens (TAA)
What are features of tumour specific antigens?
- Are only found on tumours
- As a result of point mutations or gene rearrangement
- Derive from viral antigens
What are features of tumour associated antigens?
- Found on both normal and tumour cells, but are overexpressed on cancer cells
- Developmental antigens which become derepressed (CEA)
- Differentiation antigens are tissue specific
- Altered modification of a protein could be an antigen
What is evidence for human tumour immunity?
- Spontaneous regression: melanoma, lymphoma
- Regression of metastases after removal of primary tumour: pulmonary metastases from renal carcinoma
- Infiltration of tumours by lymphocytes and macrophages: melanoma and breast cancer
- Lymphocyte proliferation in draining lymph nodes
- Higher incidence of cancer after immunosuppression, immunodeficiency (AIDS, neonates), aging, etc
What is evidence of escape?
- Tumour escape
- Immune evasion
What is tumour escape?
Immune responses change tumours such that tumours will no longer be seen by the immune system
What is immune evasion?
Tumours change the immune responses by promoting immune suppressor cells
What are the 2 types of immunotherapy?
- Active
- Passive
What is an example of active immunotherapy?
Vaccination
What are the different types of vaccines?
- Killed tumour vaccine
- Purified tumour antigens
- Professional APC (antigen presenting cells, types of WBC) -based vaccines
- Cytokine- and costimulator- enhanced vaccines
- DNA vaccines
- Viral vectors
What are 2 examples of passive immunotherapy?
- Adoptive Cellular Therapy (T cells)
- Anti-tumour Antibodies (Her-2/Neu, CD20, CD10, CEA, CA-125, GD3 ganglioside)
What is cell-based therapy?
- Cellular therapies can be used to activate a patient’s immune system to attack cancer
- They can also be used as delivery vehicle to target therapeutic genes to attack the tumour
- They do not act directly on cancer cells
- work systemically to activate the body’s immune system
What is a dendritic cell?
An antigen presenting cell
What is the precursor to dendritic cells?
Monocytes
Where do macrophages accumulate?
Hypoxic areas
What is tumour hypoxia?
- Hypoxia (low oxygen) is a prominent feature of malignant tumours
- Inability of the blood supply to keep up with growing tumour cells
- Hypoxic tumour cells adapt to low oxygen
What are the problems with hypoxia?
- Stimulates new vessel growth
- Suppresses immune system
- Resistant to radio/chemotherapy (repopulate the tumour)
- Increased tumour hypoxia after therapy
