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Cytokines: A cast of molecular characters in search of their roles. Cytokines in Cancer Therapy by Frances R. Balkwill. Oxford University Press, 1989. Pp. 297. £30

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Page 1: Cytokines: A cast of molecular characters in search of their roles. Cytokines in Cancer Therapy by Frances R. Balkwill. Oxford University Press, 1989. Pp. 297. £30

a Ciba Symposium on this particular topic. New mol- ecular biological approaches, together with the use of synthetic oligosaccharide probes, are likely to yield much new information in the next few years and therefore it would perhaps have been more profitable to hold the meeting after some of these studies have been performed. In this way, the practicalities and strategies of these technologies could have been disseminated and participants and readers would have gained a new insight into oligosaccharide function. This is exemp- lified in the Chairman’s summing-up, where he is not convinced, even after the meeting, that the defined functions of certain carbohydrates have been ad- equately demonstrated. I concur with him that we will know much more once we have used new techniques to study the functional consequences of adding, deleting, or changing oligosaccharide structure.

Martin J. Humphries is at the Department of Biochemistry and Molecular Biology, University of Manchester, Manchester M13 9PT, UK.

Cytokines: A Cast of Molecular Characters In Search of Their Roles Cytokines in Cancer Therapy by Frances R. Balkwill. Oxford University Press, 1989. Pp. 297. 530. By Alan Morris It is a sad fact that, despite immense effort, the efficacy of therapy for most cancers has barely improved over the past decades. Such improvements in survival that we have seen have been largely due to better patient care, and perhaps earlier diagnosis. Many cancer physi- cians and scientists now accept that significant new treatments are unlikely in the medium term, and that for the long term our understanding of what is cancer and the host’s response must be refined very consider- ably before we can expect a real change in this gloomy situation. This present book, a review of the biology of some cytokines and their real and potential use in cancer therapy, illustrates just how difficult it is to make any real progress in understanding cancer and host responses to it. In science we often find that confusion and muddle is cleared up when some grand generalisa- tion appears, so that disorganized data can be fitted together to form a coherent theory. This certainly happens in the biological sciences but I very much fear that as we do more and more research into cytokine biology we move away from any sort of clarity; the system is just too complex.

Cytokines are a hotch-potch of protein factors which have effects on cell physiology rather like hormones but distinguished from these by their not being produced by specialized organs. We have made the assumption that cytokines are important in resistance to disease, includ- ing cancer, and so there is huge interest in their possible therapeutic use.

One of the general triumphs of modern molecular

genetics has been gene cloning and, with respect to cytokines, this has given us detailed molecular descrip- tion of several cytokines. Thus we know, for example, that interferon beta is a protein of precisely 187 amino acids. Move away from this kind of certainty and we enter a morass.

It seems to me that the greatest problem is in knowing, not what cytokines do, but what they are for. There are two levels of difficulty. One is that cytokines show a bewildering range of in vitro biological proper- ties, varying with cell system studied, and the other is that cytokines interact with one another, again variably. I am convinced that many cytokine actions and interac- tions are artefactual, or at least of very limited rel- evance, but I do not know which, and I would welcome guidance. It is extremely hard to make a judgement of which cytokine actions matter most (or matter at all) but criteria which could be employed would include: 1, generality of an effect, reported for different cell systems and by more than one research group; 2, high specific activity of the cytokine for the effect; 3, a good rationalization for the importance of the effect in a disease situation; 4, a clear demonstration that the cytokine plays a role in resistance to that disease. Of course, this is a counsel of perfection and can only rarely be achieved, as, for instance, in the demon- stration of the importance of macrophage activation by interferon gamma in certain bacterial infections. This book, unfortunately, does not make a serious attempt to judge the importance of different cytokine actions in physiological or disease processes. This is a pity, be- cause, hard though it may be to achieve, this judgement is what is needed, and I would have hoped that Franni Balkwill would be the person with the experience and background to have made it. Instead, the book seems filled with lists of unweighted facts and observations.

The book is entitled Cytokines in Cancer Therapy but this is somewhat misleading as, in fact, there exist significant data only for interferon alpha and these data are disappointing. The dispiriting fact is that interferon has essentially no usefulness in the treatment of the major cancers - lung, breast, bowel and so on - and those diseases that do seem to be susceptible to inter- feron therapy are rare. The best example of effective interferon alpha therapy is in hairy cell leukaemia, which is incredibly rare, and even here the data do not yet show improved survival in what is a relatively benign and slowly evolving condition. Interleukin 2 has been used indirectly in therapy through generation of lymphokine-activated killer cells, which perhaps do show some efficacy, but, by itself, interleukin 2 is of very little use in cancer. Other cytokines have either not been tested or there are so few data as to make any sort of conclusion impossible. This does seem small beer, and the bulk of the book is in fact devoted to an account of what cytokines do.

In a book of this sort, it is more difficult to know what to leave out than to know what to include. There is no

Page 2: Cytokines: A cast of molecular characters in search of their roles. Cytokines in Cancer Therapy by Frances R. Balkwill. Oxford University Press, 1989. Pp. 297. £30

real definition of the word cytokine and so what one includes must be a personal choice. If only those cytokines which have been tried in cancer therapy were included, the bulk of the book would be concerned with the heavily worked-over interferons. Dr Balkwill has chosen to be comprehensive, and so there are chapters on 'The other interleukins', 'The colony stimulating factors', 'Transforming growth factor.. .' which are not yet tried in cancer therapy -but might be. In addition to these, there are chapters on the interferons, interleukin 2 and lymphokine-activated killer cells, and tumour necrosis factor. The book is prefaced by a chapter on

principles of cytokine therapy (I wish there were such) and there are concluding chapters on the cytokine network and future directions. A compensating strength is thus that it is a very detailed account and is well illustrated with line drawings and photographs of great cytokine-ologists. I suspect that it will be a standard reference book for at least a little while.

Alan Morris is in the CRC Interferon & Cellular Immunity Research Group, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, 1 UK. 1