Implications of macrophage T-lymphocyte interactions for tumor rejectability

Abstract

A relatively detailed model of experimentally described macrophage T-lymphocyte interactions has been developed. In this model we investigate the immune response to tumors that differ in antigenicity and/or in initial slee. Having deliberately omitted from the model tumor escape mechanisms (e.g. suppression, antigenic modulation or heterogeneity), we study the circumstances that nevertheless lead to progressive tumor growth. The model behavior shows that: (1) tumor antigenicity can best be defined in terms of helper T cell reactivity; (2) small differences in the availability of HTL (*) markedly influence tumor rejectability; (3) compared with the impact of macrophages, the impact of CTL increases more with increasing tumor antigenicity; and (4) sneaking through and tolerance are intrinsic to this model. HTL have a large impact on the model behavior ( i.e. the immune response) because there are self-reinforcements in the HTL activation and proliferation process. Interestingly, unresponsiveness (tolerance) evolves in this model, despite the precense of these self-reinforcements end the absence of negative interactions (e.g. suppression). Tolerance ie caused by a proliferation threshold that comes into existence when T-lymphocyte effectors are made short-lived. We discuss the advancages of using numerical integration combined with numerical phase state analysis. Stable steady states in this model do exist but are of minor importance