Tumour immunology

Question 1

Tumour development

Answer 1

Single cell develops altered growth properties
Cell proliferates to form a benign tumour
Tumour becomes invasive (malignant)
Metastatic tumour invades vessels/lymphatics and spreads

Question 2

Cancer types

Answer 2

Carcinomas develop from epithelial origins
Sarcomas from mesodermal connective tissue
Lymphomas, myelomas and leukaemias from haematopoietic stem cells

Question 3

Malignant transformation

Answer 3

Process by which a normal cell acquires properties of a tumour cell (can be benign or malignant)

Can be initiated by exposure to carcinogens that damage DNA (UV light, smoke), or infection with viruses (HPV, Epstein-Barr virus)

May be genetic pre-disposition (BRCA1)

Question 4

Cancer-associated genes

Answer 4

Proto-oncogenes promote cell proliferation. Mutated or overexpressed to oncogenes which promote uncontrolled growth
Tumour suppressor genes inhibit proliferation and can be mutated or lost
Apoptosis regulators control programmed cell death

Question 5

Tumour antigens

Answer 5

Tumour specific antigens are unique to the tumour (mutated oncogenes, viral proteins including HPV E6)

Tumour associated antigens are normal proteins that are over expressed in cancer cells. HER2 oncogene in breast cancer

Question 6

Tumour detection by immune system

Answer 6

TSA or TAA antigens are presented on MHCI of tumour cells
Replication stress and DNA damage can also cause expression of NK ligands
DCs/macrophages present antigens to B and T cells and secrete cytokines such as TNF-a (tumour necrosis factor)

Tumour cells killed by NK cells, inflammatory macrophages and CTLs

Question 7

Immunoediting

Answer 7

Immunosurveillance kills tumour cells (elimination)
Immune system restricts tumour growth (equilibrium)
Selection pressure causes growth of tumour cells that are not sensitive to immune attack (escape)

Inflammatory microenvironment may also promote tumour growth

Question 8

Immune evasion

Answer 8

Not all cancer cells express appropriate antigens for detection
May lack co-stimulatory CD80/86 (T cell activation)
Genetic mutations and immunoediting

Question 9

Immunotherapy

Answer 9

Initiate and supplement the anti-tumour immune response

Promote a strong tumour-specific CTL response
Antibodies used to target drugs to cancer cells

Question 10

Monoclonal antibodies

Answer 10

Generated in mouse hybridoma cell lines (all have same specificity)

Humanised antibodies modified to be more similar to our own antibodies.
Herceptin against HER2 breast cancers
Rituxan against B cell marker CD20 (non-hodgkins lymphoma)

Question 11

ADCs

Answer 11

Antibody Drug Conjugates

monoclonal antibodies couples to toxins, drug molecules or radioisotopes to kill tumour cells

Question 12

Antibodies against surface receptors

Answer 12

Block growth factor receptors. Herceptin blocks HER2

Block vascular endothelial growth factor signalling. Inhibits growth of blood vessels around the tumour

Question 13

Immune checkpoint inhibitors

Answer 13

Antibodies block binding of co-inhibitory receptors on T cells, releasing T cell inhibition.

Antibodies against CTLA-4 block CD80/86 binding
Antibodies against PD-L1 or PD-1 block binding of PD-1 to PD-L1

Question 14

CAR therapy

Answer 14

Chimeric Antigen Receptor T cell therapy
Patient T cells isolated and CAR gene inserted.
Tumour specific CAR T cell re-infused into patient
May induce cytokine release syndrome

Question 15

Therapeutic vaccines

Answer 15

Virus based vaccines express cancer antigens and co-stimulatory molecules

Cell-based therapies involve immune cells isolated from patient, stimulated to respond to tumours and injected back into the body