Presentation Title

Keeping T Cells Young and Fabulous: Modulating Metabolic and Developmental Pathways to Promote a Memory Phenotype

Faculty Mentor

Yukiko Yamaguchi, Saul J Priceman, Stephen J Forman

Start Date

18-11-2017 2:15 PM

End Date

18-11-2017 3:15 PM

Location

BSC-Ursa Minor 115

Session

Poster 3

Type of Presentation

Poster

Subject Area

health_nutrition_clinical_science

Abstract

T cell immunological efficacy is rooted in the ability to sustain a memory response to pathogens. Upon antigen encounter, naïve T cells differentiate into stem cell memory T cells (TSCM) and central memory T cells (TCM) which exhibit self-renewal capabilities to enable a long-lasting memory response . In adoptive T cell therapies, one of the challenges to effectively combating cancers involves limitations surrounding methods for ex vivo T cell expansion which favor memory phenotypes (Priceman et al., 2015). Considering this it is important to explore potential pharmacological means of promoting T cell stemness. Here, we evaluated modulators of 4 different pathways in order to ascertain whether inhibition or agonization of different pathways enhances T cell stemness. By in vitro phenotyping T cells via flow cytometry, we assessed which agonists and antagonists affected stem-like marker presentation on the surface of T cells over the course of 28 days while considering expansion and overall viability. Agonistic modulation of pathway 1 exhibited potential for memory phenotype promotion. Agonists of pathway 2 did not hinder growth at our working concentrations while antagonists accelerated exhaustion. Modulator X accelerated differentiation and modulator Y did not affect phenotype at our working concentrations. These pathways function in T cell differentiation and can be manipulated in vitro to maintain a TSCM/TCM phenotype.

Summary of research results to be presented

•Pathway 1’s modulator A showed indications of maintaining a memory phenotype but inhibited cellular growth at 10 µM. •At concentrations that did not cause rapid cell death, pathway 2 agonists (modulators B, C) did not impact TSCM/TCM phenotype while antagonists (modulators D, E) promoted an effecter phenotype (data not shown). •Pathway 3’s modulator X differentiated T cells and decreased proliferation in a dose-dependent manner. •Pathway 4’s modulator Y made marginal impact on T cell differentiation at our working concentrations.

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Nov 18th, 2:15 PM Nov 18th, 3:15 PM

Keeping T Cells Young and Fabulous: Modulating Metabolic and Developmental Pathways to Promote a Memory Phenotype

BSC-Ursa Minor 115

T cell immunological efficacy is rooted in the ability to sustain a memory response to pathogens. Upon antigen encounter, naïve T cells differentiate into stem cell memory T cells (TSCM) and central memory T cells (TCM) which exhibit self-renewal capabilities to enable a long-lasting memory response . In adoptive T cell therapies, one of the challenges to effectively combating cancers involves limitations surrounding methods for ex vivo T cell expansion which favor memory phenotypes (Priceman et al., 2015). Considering this it is important to explore potential pharmacological means of promoting T cell stemness. Here, we evaluated modulators of 4 different pathways in order to ascertain whether inhibition or agonization of different pathways enhances T cell stemness. By in vitro phenotyping T cells via flow cytometry, we assessed which agonists and antagonists affected stem-like marker presentation on the surface of T cells over the course of 28 days while considering expansion and overall viability. Agonistic modulation of pathway 1 exhibited potential for memory phenotype promotion. Agonists of pathway 2 did not hinder growth at our working concentrations while antagonists accelerated exhaustion. Modulator X accelerated differentiation and modulator Y did not affect phenotype at our working concentrations. These pathways function in T cell differentiation and can be manipulated in vitro to maintain a TSCM/TCM phenotype.