Assessment of cancer immunotherapy outcome in terms of the immune response time features

Abstract

A cytokine-based periodic immunotherapy treatment is included in a model of tumour growth with a delay. The effects of dose schedule are studied in the case of a weak immune system and a growing tumour. We find the existence of 'metastable' states (that may last for tens of years) induced by the treatment and also potentially adverse effects of the dosage frequency on the stabilization of the tumour. These two effects depend on the delay between the tumour growth and the immune system response, the cytokine dose burden, and other parameters considered in the model.

An immune system–tumour interactions model with discrete time delay: Model analysis and validation

“…in [24]. Clearly, in the literature [15,17,18] discrete delay in the variable representing the size of the immune system was also considered. However, this idea is not followed since the priority is given to the immune system's time reaction.…”

“…However, to better understand the main underlying mechanism of immune response to the presence of the tumour cells complex models were simplified and thus reduced into two-or three-equation and less detailed ones, see e.g. [13][14][15][16][17][18][19] or [20][21][22][23][24][25][26].…”

Radioterapia y el papel del sistema inmunitario

“…A reference protocol was simulated in [1] while coefficients entering equation 3 were varied at random among admissible values [11]. The simulation, then, covers a wide range of tumors and supply general results useful to clinical practice.…”

“…(3). Numerical estimation of these coefficients was already made in [11] (and also in [8] values have been drawn randomly from a log-normal distribution, to avoid negative values, but keeping the immune system efficiency ( /   ) always smaller than 1. Survival factors [19,22] are also taken as random values.…”

“…Such models have been used to explain and to describe immune depression effects [9], the role of time delays in immune response [10,11], radiovirotherapy treatments [12], chemotherapy treatments [13] and even surgery [14].…”