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Issue 284: Traditionally, therapies have been combined with immunotherapy without much consideration of how each component part impact the immune system. For example, the figure depicts the tumour-immune state of a hypothetical patient in the top left corner (red – cancer cells, blue – immune cells) and the impact of therapy thereon. Treatment with either radiation, chemotherapy or targeted agents results in a small tumour and suppressed immune system (leftwards, down arrow). Subsequent administration of immune-checkpoint-inhibitors may change the underlying immune properties (leftward arrow), but not in a manner that is sufficient to push the patient into the region of tumour control (green shaded region). Despite potentially having treatment options available, the toxicity profile of the patient may preclude their use. In this paper we argue that mathematical modelling is a useful tool to visualize the effects of various therapies on the tumour-immune state; and conceptualize how to rationally combine therapies, to best play the so-called immunotherapy numbers game.