Tumour immune response

The science of immunology not only encompasses the body s immune responses to bacteria and viruses but is extensively involved in tumour recognition and subsequent rejection the rejection of transplanted organs and tissues the elimination of parasites ftom the body allergies and autoimmunity (the condition when the body mounts a reachon agairrst its own tissues). 

Naturally occurring tumours evoke little or no immune response in experimental animals. This is disappointing but it must be remembered that these cells have already escaped the normal immune surveillance. 

Transformed cells expressing tumour-specific surface antigens that closely resemble normal surface antigens may not induce an immune response. Furthermore, some tumour antigens, although not usually expressed in adults, were expressed previously during the neonatal period (i.e. just after birth) and are thus believed by the immune cells to be self . 

Although several of the strategies listed in Table 14.5 are being employed in these trials, many focus upon the introduction of various cytokines into the tumour cells themselves in order to attract and enhance a tumour-specific immune response. 

The cells are called natural killer cells since they kill without a requirement for MHC class I or class II proteins. This characteristic is sometimes termed the MHC-independent immune response. Their principal role is in defence against virnses and other intracellular microorganisms that is, they kill host cells infected with a vims or other pathogen. They also kill tumour cells. Thus they have a role in the process of immune surveillance for tumour cells. 

Mechanism of action is not clearly understood but direct antiproliferative action against tumour cells and modulation of the host immune response may play important roles. 

Fig. 9.2. Simplified schema of the development of T helper type 1 (Th1) and 2 (Th2) cells under the influence of interleukin (IL)-12 and IL-4, respectively, and how these two polarized T cell phenotypes produce cross-inhibitory cytokine profiles and promote different aspects of the host immune response (IFNy, interferon-gamma TNFa, tumour necrosis factor alpha Thr, T helper regulatory cell Th3, T helper type 3 cell).

Mechanism of Action. Although the details are unclear, imiquimod enhances the local production of interferons, tumour necrosis factor-alpha, and possibly other cytokines that produce antiviral responses. Hence, this drug does not act directly on the virus, but instead modulates the host (human) immune responses that have antiviral effects. 

As well as being used as producers of chemicals, cells themselves can be cultured and then reintroduced into the animal in an attempt to cure a disease or repair tissue damage. For instance lymphocytes, stimulated to grow in vitro, can be used to improve the immune response to tumours. 

A quite unusual antimetabolite is the enzyme L-asparagi-nase, isolated from E. coli, commonly used in the treatment of leukemia. Asparagine is a precursor of purine synthesis (Voet Voet have all the details), and depletion of this amino acid seems to slow down tumour cells. One could speculate at length why this would have a preferential effect on tumour cells, but it may be better not. Of note, this drug can be used for extended periods of time without inducing a neutralizing immune response (which it normally should) because the immune system will be quite knocked out under the prevailing conditions of disease and treatment. 

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