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We thank Dr Ann Johnson (August 2002 JRSM1) for her thoughtful comments on our paper2. She rightly points out the similarity between the hypoxic centres of tumours and tubercles and the likelihood that potentially proliferative cancer cells are sequestered in the former, until released by resorption of the core tissues. Until recently, this was the accepted model of persistence of supposedly dormant tubercle bacilli in tuberculous scars. It has, however, now been shown by in-situ PCR that DNA specific for Mycobacterium tuberculosis is widely distributed throughout normal lung tissue in those latently infected by this organism3. Thus, it is likely that reactivation of tuberculosis occurs more often from these ‘infective micrometastases’ than from healed primary foci of infection. In both diseases, immune elimination of micrometastases may be as important as, or more important than, containment of reactivating primary lesions.
Concerning variation in growth rates of tumours, we are aware of the time taken for a single cell to develop into a clinically or radiologically evident tumour and the implications for follow-up in immunotherapeutic studies, which needs to be long-term. We would, however, like to make two observations.
First, tumours do not arise simply by steady cell proliferation, but by a highly dynamic process involving cell replication and cell destruction by apoptosis and other immune-mediated mechanisms4. Indeed, tumour growth may be more attributable to a failure of apoptosis than to more rapid cell replication. If the immune destruction of cancer cells, aided by effective immunotherapy, balances the growth of the cells, the patient remains for practical purposes healthy.
Second, reported immune responses, whether occurring as a result of natural infection or specific immuno-therapeutic strategies, have not just led to delays in tumour growth but in some cases to regression of even very large tumours and to long periods of subsequent health.
Ideally, immunotherapy would eradicate all tumour cells but even if it only prevented the overall increase of a clinically undetectable tumour load the result for the patient would be highly beneficial. Perhaps the future trend in oncology will be to enable patients to live contentedly with their tumour residues after local debulking rather than to submit them to physically damaging and psychologically stressful attempts at radical ‘cure’.