Tumor escape from immune elimination

Abstract

A simple kinetic model is proposed for the interaction between a tumor and the immune system. Special attention is given to the phenomenon of “sneaking through” and the associated phenomena of tumor regression and recurrence. Sneaking through refers to the situations in which small antigenic tumors grow progressively, medium-sized tumors are rejected and large ones break through again. The combination of two factors is proposed as being essential for explaining this behavior: (a) The dependence of the immune response on antigen dose. (b) The negative intervention of immunosuppressors, or inhibitory factors. The immune response is described here as a repeated antigen-dependent stimulation of lymphoid cells to proliferate, with a parallel process of antigen-dependent differentiation to a terminal phase. For too small or too large antigen doses the growth in the number of cells is counter-balanced by loss from the proliferative pool through natural decay or by enhanced differentiation, respectively. When this is combined with the blocking of resting and proliferating precursor cells by factors originating from tumor cells, computer simulations demonstrate that the model is able to account for the observed patterns of tumor behavior. The model allows for a discussion of the significance of various biological parameters and is amenable for testing.