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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 cellmediated immune response, there is an increased risk for tumour development.
Similarly, in individuals with acquired immune deficiency (HIV/AIDS or druginduced) there is an increased risk for tumour development.

IMMUNOTHERAPY
Principles
Attempts may be made to eliminate tumours with the use of immune methods. These
include:
1.

Active immunization
Utilization 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 bullet


In 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.

Questions
1.

BCG therapy for tumours utilizes the principle of?


(a)
(b)
*(c)

Active immunization
Passive immunization
Non-specific enhancement of immunity
2

2.

(d)
Direct toxicity by BCG on tumour cells
Which of the following is NOT associated with an increased risk of tumour
development?
(a)
*(b)
(c)
(d)

Di George syndrome
Congenital hypoimmunoglobululinaemia
HIV/AIDS
Chemotherapeutic drugs

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