D1chotamous immune response to cancer: CO-adaptation and control

The limited benefit achieved thus far from immunotherapeutic approaches to cancer therapy calls for a reassessment of the prevailing view that the tumorimmune system relationship is entirely adversarial in nature. Potentially immunogenic tumors often fail to elicit effective immune responses. It is usually concluded that the immune response is defective or suppressed. We propose that the fundamental mode of the immune response to tumors is adaptation rather than rejection. Our analysis rests on the concept of a dichotomy in the immune response to an acute versus chronic perturbance. At the cellular level, this dichotomy is related, in particular, to the recently recognized existence of different levels of T-cell "activation" and of alternative ways in which antigenic challenges are controlled by the immune system. The variability of the functional phenotype may reflect environmental tuning of the cell's activation thresholds for different functions (Grossman& Paul, PNAS 89, 10365-39, 1992). Tumor-infiltrating cells may have a dual effect on cancer progression, simultaneously supporting tumor cell viability and limiting the rate of tumor growth. Concomitant, central immunity is more likely to play a role in surveillance, especially in the control of metastasis.