Table 1.

Description of the model.

Component	Variable	Type	Governing equations
Tumor cells	NC	Agent-based	${\rho }_P=p\left(1+{\delta }_P{\mathrm{\Delta }}_P\right)\left(1-\zeta {\mathrm{\Delta }}_{\mathrm{MGA}}\right)\frac{1}{1+N_C/K_0}\left(1\text{a}\right)$ ${\rho }_A=d_C\left(1-{\delta }_A{\mathrm{\Delta }}_A\right)\left(1\text{b}\right)$ ${\rho }_{\mathrm{NK}}={\delta }_{\mathrm{MUT}}\frac{N_{\mathrm{NK}}}{\frac{N_C}{K_1}+N_{\mathrm{NK}}}\frac{E_{\mathrm{NK}}}{1+\frac{N_{\mathrm{Treg}}}{K_2}}\left(1-{\delta }_{\mathrm{IE}}{\mathrm{\Delta }}_{\mathrm{IE}}\right)\left(1-\zeta {\mathrm{\Delta }}_{\mathrm{MIE}}\right)\left(1\text{c}\right)$ ${\rho }_R=1+\zeta p\left(1+{\delta }_P{\mathrm{\Delta }}_P\right){\mathrm{\Delta }}_{\mathrm{MGA}}\frac{1}{1+N_C/K_0}\left(1\text{d}\right)$
NK cells	NNK	ODE	$N_{\mathrm{NK}}^{\prime }={\sigma }_{\mathrm{NK}}-d_{\mathrm{NK}}{N}_{\mathrm{NK}}\left(2\right)$
CTLs	NCTL	ODE	$N_{\mathrm{CTL}}^{\prime }={\sigma }_{\mathrm{CTL}}{N}_{\mathrm{MUT}}^{*}-d_{\mathrm{CTL}}{N}_{\mathrm{CTL}}\left(3\right)$
Tregs	NTreg	ODE	$N_{\mathrm{Treg}}^{\prime }={\sigma }_{\mathrm{Treg}}{N}_{\mathrm{MUT}}^{*}\frac{\tau }{1+\tau /K_4}-d_{\mathrm{Treg}}{N}_{\mathrm{Treg}}\left(4\right)$
TGF-β	τ	Algebraic	τ = τMUTNMUT + τTregNTreg(5)

Tumor cells (N_C) are modeled discretely as agents; all other variables are modeled continuously. Each tumor cell exists in one of 2³ states by mutation profile, see Methods for description.