title: Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion.
abstract: T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in 'chase-and-escape' dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.
authors.affiliation: Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan Cedex, France.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Lorenzi
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Chisholm
authors.affiliation: Department of Health Sciences, A. Avogadro Università del Piemonte Orientale, Novara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Melensi
authors.affiliation: MAMBA Team, INRIA-Paris-Rocquencourt, Le Chesnay Cedex, France.|Laboratoire Jacques-Louis Lions, Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Paris, France.|Laboratoire Jacques-Louis Lions, CNRS, UMR 7598, Paris, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lorz
authors.affiliation: Department of Mathematical Sciences, Politecnico di Torino, Torino, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Delitala
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D016923:Cell Death; D049109:Cell Proliferation; D003198:Computer Simulation; D006801:Humans; D057131:Immune Evasion; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D018448:Models, Immunological; D009716:Numerical Analysis, Computer-Assisted; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D000941:Antigens
keywords: T cells; mathematical modelling; memory; theoretical immunology; vaccination