Heterogeneous cell populations form an interconnected network that determines their collective output. One example of such a heterogeneous immune population is tumor infiltrating lymphocytes (TILs), whose output can be measured in terms of its reactivity against tumors.
hile the degree of reactivity varies considerably between different TILs, the underlying network that governs the reactivity is poorly understood. We asked whether one can predict and even control this reactivity. We addressed this by accurately measuring subpopulation compositions of 91 TILs surgically removed from 27 metastatic melanoma patients. Despite the large number of subpopulations compositions, we were able to computationally extract a simple set of subpopulation based rules that accurately predict the degree of reactivity.
This raised the conjecture of whether one could control reactivity of TILs by manipulating their subpopulation fractions. Remarkably, by rationally enriching and depleting selected subsets of subpopulations we were able to restore anti-tumor reactivity to non-reactive TILs.
Altogether, this work describes a general framework for predicting and controlling the output of a cell mixture.
Oved K., Eden E., et al, Mol Syst Biol. 2009;5:265. Epub 2009 Apr 28.