Immunotherapy in genitourinary neoplasia

An overview of these results gives the impression that immunotherapy has at best achieved only limited success in the management of neoplasia. Several factors may account for this. First, most attempts have involved direct manipulation of only one of many immune response mechanisms while disregarding their various interactions both between themselves and the developing tumor. In reality, however, such manipulation may actually evoke many, often competitive responses. Only now are we becoming aware of this complexity. Clearly, the checks and balances that influence the final expression of these effects, and the response of the tumor as well in modifying or abrogating host defense mechanisms, must be taken into account in the design of any immunotherapy approach. In addition, there is increasing evidence that cells in a particular tumor are heterogeneous and probably polyclonal. The possible existence of both antigenic heterogeneity and heterogeneous susceptibility to cytolysis by immune response mechanisms may introduce a degree of complexity for both recognition and effector aspects of immune reactivity that is difficult if not impossible to surmount by presently available immunotherapeutic techniques. Finally, it is likely that antigenicity, immunogenicity, and biologic behavior may vary between different tumors in different patients. Moreover, patients themselves may vary in their immunologic capability in general and specifically in relation to their developing tumor. Methods that are presently available for classification of tumors according to their immunogenicity and potential response of immunotherapy as well as for classification of patients according to the effectiveness of their immune response reactivity are presently undeveloped. Such factors, however, warrant study if appropriate application of immunologic intervention is to become clinically useful. The design of future investigations must take into account considerations such as these and recognize as well the necessity to conduct randomized prospective trials of such approaches because of the unpredictable natural history of tumor behavior in an individual patient. Certainly, clinical failures due to distant metastatic disease imply the urgent need for the development of effective systemic therapy in order to successfully assist regional surgery in the containment of developing tumors, and to provide a means whereby already disseminated disease can be abolished.