The progressive growth of tumor induces a major alteration in the immune response which could have significant deleterious consequences on the outcome of immunotherapeutic strategies. A more complete understanding of the mechanisms involved and the clinical consequences of these alterations is necessary to determine the importance of such changes. It is possible however, that the analysis of the TCR sigma chain or other signal transduction elements can be a more informative way to monitor the therapeutic effects of a particular treatment than the functional immunologic assays on peripheral blood lymphocytes used presently. Ultimately understanding this phenomenon could help determine the treatment approaches that would prevent or reverse the state of altered immune response, allowing for the development of more effective cancer treatments. It is clear that there are a number of barriers to successful immunotherapy (Table 4-1). Each difficulty has a number of potential solutions. It seem likely that as each of these known barriers is overcome, a larger number of patients will benefit than do now from the current generation of treatment approaches. Of course, it is also likely that there are additional barriers to success yet to be uncovered. It is only through careful observation and monitoring of the clinical effects of our interventions that the remaining obstacles will be defined. And it is only through the close interaction of the laboratory and the clinic that novel solutions will be devised.