Open AccessPredicting and controlling the reactivity of immune cell populations against cancer
Author(s) -
Oved Kfir,
Eden Eran,
Akerman Martin,
Noy Roy,
Wolchinsky Ron,
Izhaki Orit,
Schallmach Ester,
Kubi Adva,
Zabari Naama,
Schachter Jacob,
Alon Uri,
MandelGutfreund Yael,
Besser Michal J,
Reiter Yoram
Publication year - 2009
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2009.15
Subject(s) - reactivity (psychology) , biology , immune system , melanoma , population , metastatic melanoma , immunology , set (abstract data type) , cancer research , computer science , medicine , pathology , alternative medicine , environmental health , programming language
Heterogeneous cell populations form an interconnected network that determine 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. While the degree of reactivity varies considerably between different TILs, ranging from null to a potent response, the underlying network that governs the reactivity is poorly understood. Here, we asked whether one can predict and even control this reactivity. To address this we measured the 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 composition. Remarkably, by rationally enriching and depleting selected subsets of subpopulations, we were able to restore anti‐tumor reactivity to nonreactive TILs. Altogether, this work describes a general framework for predicting and controlling the output of a cell mixture.