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