TUMOUR IMMUNOLOGY

TUMOUR IMMUNOLOGY

Professor B. Hanchard

OBJECTIVE:

1.TO UNDERSTAND THE BASIC PRINCIPLES RELATED TO THE ROLE OF IMMUNITY IN THE DEVELOPMENT OF CANCERS

2.TO UNDERSTAND THE ROLE OF IMMUNOTHERAPY IN THE TREATMENT OF CANCERS

OBJECTIVE: The immune surveillance theory of cancer suggests that the immune system constantly removes neoplastic cells/clones from the body when they are recognized as non-self or foreign. If the immune system is compromised for any reason this culling function becomes ineffective, allowing neoplastic cells/clones to proliferate. In support of the theory of immune surveillance are the following:1. Tumours are common at the extremes of age: In the young whose immune system is not fully developed; in the old whose immune system is undergoing involution.2. Tumours are common in those with immune deficiency either congenital or acquired through infection or drugs.

Tumour cells may express antigens that are recognized by the immune system e.g. HLA, tissue specific, retrogenetic, blood group, virus encoded and differentiation antigens. While these antigens may generate an immune response this may not be sufficient to eliminate the tumour. Tumour cells often escape the immune surveillance system. Cells may shed their surface antigen, may invert antigens into the cytoplasm or produce blocking antibodies with regard to humoral immunity. Tumour cells may also escape immune surveillance by promoting tolerance in the presence of antigen excess. Cell-mediated immunity (cytotoxic T-lymphocytes) is thought to be the major mechanism at work against the proliferation of tumour cells but humoral immunity may also play a role. A third mechanism involves natural killer cells binding to tumour antigens. In the diGeorge syndrome where individuals are born without a thymus and therefore do not generate T-cells for an effective cell-mediated immune response, there is an increased risk for tumour development. Similarly, in individuals with acquired immune deficiency (HIV/AIDS or drug-induced) there is an increased risk for tumour development.IMMUNOTHERAPY

PrinciplesAttempts may be made to eliminate tumours with the use of immune methods. These include:

1. Active immunizationUtilization of a vaccine using tumour cells whose immunogenecity has been eliminated by prior irradiation.2. Passive immunization

Injecting serum containing antibodies to tumour cells in order to induce humoral immunity.

3. Non-specific enhancement of immunity

The activation of NK cells, T-cells and macrophages e.g. BCG vaccination, interferon and IL 2.4. Monoclonal magic bulletIn this method a magic-bullet is created by linking a toxin/poison to monoclonal antibody which when injected will target specific antigen on tumour cells resulting in their death e.g. anti tac (antibody) with yttrium (toxin) in the treatment of Adult T-cell leukemia where the neoplastic lymphocytes express the tac antigen. Note that methods 1, 2 and 3 have been tried and proven unsuccessful in humans but method 4 (monoclonal magic bullet) appears to have potential as a successful treatment protocol.Questions1. BCG therapy for tumours utilizes the principle of?(a) Active immunization

(b) Passive immunization

*(c) Non-specific enhancement of immunity

(d) Direct toxicity by BCG on tumour cells

2.Which of the following is NOT associated with an increased risk of tumour development? (a)Di George syndrome*(b)Congenital hypoimmunoglobululinaemia (c)HIV/AIDS

(d)Chemotherapeutic drugsPAGE 1