title: Predicting and controlling the reactivity of immune cell populations against cancer.
abstract: 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.
authors.affiliation: Department of Biology, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Kfir
authors.initials: K
authors.lastname: Oved
authors.forename: Eran
authors.initials: E
authors.lastname: Eden
authors.forename: Martin
authors.initials: M
authors.lastname: Akerman
authors.forename: Roy
authors.initials: R
authors.lastname: Noy
authors.forename: Ron
authors.initials: R
authors.lastname: Wolchinsky
authors.forename: Orit
authors.initials: O
authors.lastname: Izhaki
authors.forename: Ester
authors.initials: E
authors.lastname: Schallmach
authors.forename: Adva
authors.initials: A
authors.lastname: Kubi
authors.forename: Naama
authors.initials: N
authors.lastname: Zabari
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
authors.forename: Yael
authors.initials: Y
authors.lastname: Mandel-Gutfreund
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Besser
authors.forename: Yoram
authors.initials: Y
authors.lastname: Reiter
mesh_terms: D002469:Cell Separation; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology*