Tumour Immunology

Prof Anura Weerasinghe

Objectives
Tumour antigens Immune surveillance against tumour cells

Tumour antigens
tumour antigens are less immunogenic than microbial antigens May be used as tumour markers May be used as targets for tumour vaccines May be used as targets for antibodies and effector T cells generated against these antigens (Immunotherapy)

Types of tumour antigens

Mutated self protein
In melanoma

Product of oncogene Her-2/neu in breast cancer Products of mutated tumour suppressor gene p53 in colon, breast & lung cancers

Carcinogenesis Chemical Physical

Defect in DNA

Biological

Types of tumour antigens

Mutated self protein
In melanoma

Product of oncogene Her-2/neu in breast cancer Products of mutated tumour suppressor gene p53 in colon, breast & lung cancers Aberrantly expressed self protein onco-foetal antigens

Oncofetal antigens
Although highly associated with some tumours, both on their cell surface and in the serum, oncofetal antigens are not unique to tumour cells since they are also found on cells during embryonic development and are found at very low levels in normal human serum.

Oncofetal antigens
Carcinoembryonic antigens (CEA) - GI cancers Alpha-fetoprotein - Hepatoma

Types of tumour antigens

Mutated self protein
In melanoma

Product of oncogene Her-2/neu in breast cancer Products of mutated tumour suppressor gene p53 in colon, breast & lung cancers Aberrantly self protein onco-foetal antigens Oncogenic virus
HPV in cervical cancer EBV in lymphoma / Nasopharyngeal carcinoma Hepatitis B in hepatoma

That the immune system surveys constantly for neoplastic cells and destroys them, is suggested by the observation of increased incidence of tumours of lymphoid or epithelial cells in immunodeficient animals and humans.

Immune surveillance
The immune system surveys constantly for neoplastic antigens associated with a newly developing tumour and destroys the cells bearing them.

Immune mechanisms operating against tumours

Activated macrophages NK cells Antibody and complement Antibody dependent cellular toxicity Cytotoxic T cells

Molecules involved in the first-line defense

Complements - Promote action of macrophages - lysis of the target cell
Cytokines - augment immune response Eg; INF- activate both macrophages and NK cells

Antibody mediated tumour rejection

Complement dependent cytotoxicity Antibody-dependent cellular cytotoxicity

Play a role in leukaemia

Not very effective in solid tumours

Complement mediated cytotoxicity

Mediated by antibodies Tumour cell + Antibody
Particularly IgM

Trigger classical complement pathway C3b and C5b

Opsonization

Lysis

Antibody-dependent cellular cytotoxicity

NK cells
+

Direct interaction with tumour cells

IgG
Sensitized tumour cell

Release of cytotoxic molecules eg; perforin

Discuss the role of following cells/molecules in immune response to tumours

T lymphocytes NK cells Macrophages Antibodies