Comparison of naïve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer

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Comparison of naïve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer. / Wang, Xiuli; Wong, ChingLam W; Urak, Ryan; Taus, Ellie; Aguilar, Brenda; Chang, Wen-Chung; Mardiros, Armen; Budde, Lihua E; Brown, Christine E; Berger, Carolina; Forman, Stephen J; Jensen, Michael C.

in: ONCOIMMUNOLOGY, Jahrgang 5, Nr. 1, 05.03.2016, S. e1072671.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Wang, X, Wong, CW, Urak, R, Taus, E, Aguilar, B, Chang, W-C, Mardiros, A, Budde, LE, Brown, CE, Berger, C, Forman, SJ & Jensen, MC 2016, 'Comparison of naïve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer', ONCOIMMUNOLOGY, Jg. 5, Nr. 1, S. e1072671. https://doi.org/10.1080/2162402X.2015.1072671

APA

Wang, X., Wong, C. W., Urak, R., Taus, E., Aguilar, B., Chang, W-C., Mardiros, A., Budde, L. E., Brown, C. E., Berger, C., Forman, S. J., & Jensen, M. C. (2016). Comparison of naïve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer. ONCOIMMUNOLOGY, 5(1), e1072671. https://doi.org/10.1080/2162402X.2015.1072671

Vancouver

Bibtex

@article{c8ffe81804c84e64bef40d4d895a66e8,
title = "Comparison of na{\"i}ve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer",
abstract = "Human CD8+ effector T cells derived from CD45RO+CD62L+ precursors enriched for central memory (TCM) precursors retain the capacity to engraft and reconstitute functional memory upon adoptive transfer, whereas effectors derived from CD45RO+CD62L- precursors enriched for effector memory precursors do not. Here we sought to compare the engraftment fitness and function of CD8+ effector T cells derived from CD45RA+CD62L+ precursors enriched for na{\"i}ve and stem cell memory precursors (TN/SCM) with that of TCM. We found that cytotoxic T cells (CTLs) derived from TCM transcribed higher levels of CD28, FOS, INFγ, Eomesodermin (Eomes), and lower levels of BCL2L11, maintained higher levels of phosphorylated AKT, and displayed enhanced sensitivity to the proliferative and anti-apoptotic effects of γ-chain cytokines compared to CTLs derived from TN/SCM. Higher frequencies of CTLs derived from TCM retained CD28 expression and upon activation secreted higher levels of IL-2. In NOD/Scid IL-2RγCnull mice, CD8+ TCM derived CTLs engrafted to higher frequencies in response to human IL-15 and mounted robust proliferative responses to an immunostimulatory vaccine. Similarly, CD8+ TCM derived CD19CAR+ CTLs exhibited superior antitumor potency following adoptive transfer compared to their CD8+ TN/SCM derived counterparts. These studies support the use of TCM enriched cell products for adoptive therapy of cancer.",
author = "Xiuli Wang and Wong, {ChingLam W} and Ryan Urak and Ellie Taus and Brenda Aguilar and Wen-Chung Chang and Armen Mardiros and Budde, {Lihua E} and Brown, {Christine E} and Carolina Berger and Forman, {Stephen J} and Jensen, {Michael C}",
year = "2016",
month = mar,
day = "5",
doi = "10.1080/2162402X.2015.1072671",
language = "English",
volume = "5",
pages = "e1072671",
journal = "ONCOIMMUNOLOGY",
issn = "2162-402X",
publisher = "Taylor & Francis",
number = "1",

}

RIS

TY - JOUR

T1 - Comparison of naïve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer

AU - Wang, Xiuli

AU - Wong, ChingLam W

AU - Urak, Ryan

AU - Taus, Ellie

AU - Aguilar, Brenda

AU - Chang, Wen-Chung

AU - Mardiros, Armen

AU - Budde, Lihua E

AU - Brown, Christine E

AU - Berger, Carolina

AU - Forman, Stephen J

AU - Jensen, Michael C

PY - 2016/3/5

Y1 - 2016/3/5

N2 - Human CD8+ effector T cells derived from CD45RO+CD62L+ precursors enriched for central memory (TCM) precursors retain the capacity to engraft and reconstitute functional memory upon adoptive transfer, whereas effectors derived from CD45RO+CD62L- precursors enriched for effector memory precursors do not. Here we sought to compare the engraftment fitness and function of CD8+ effector T cells derived from CD45RA+CD62L+ precursors enriched for naïve and stem cell memory precursors (TN/SCM) with that of TCM. We found that cytotoxic T cells (CTLs) derived from TCM transcribed higher levels of CD28, FOS, INFγ, Eomesodermin (Eomes), and lower levels of BCL2L11, maintained higher levels of phosphorylated AKT, and displayed enhanced sensitivity to the proliferative and anti-apoptotic effects of γ-chain cytokines compared to CTLs derived from TN/SCM. Higher frequencies of CTLs derived from TCM retained CD28 expression and upon activation secreted higher levels of IL-2. In NOD/Scid IL-2RγCnull mice, CD8+ TCM derived CTLs engrafted to higher frequencies in response to human IL-15 and mounted robust proliferative responses to an immunostimulatory vaccine. Similarly, CD8+ TCM derived CD19CAR+ CTLs exhibited superior antitumor potency following adoptive transfer compared to their CD8+ TN/SCM derived counterparts. These studies support the use of TCM enriched cell products for adoptive therapy of cancer.

AB - Human CD8+ effector T cells derived from CD45RO+CD62L+ precursors enriched for central memory (TCM) precursors retain the capacity to engraft and reconstitute functional memory upon adoptive transfer, whereas effectors derived from CD45RO+CD62L- precursors enriched for effector memory precursors do not. Here we sought to compare the engraftment fitness and function of CD8+ effector T cells derived from CD45RA+CD62L+ precursors enriched for naïve and stem cell memory precursors (TN/SCM) with that of TCM. We found that cytotoxic T cells (CTLs) derived from TCM transcribed higher levels of CD28, FOS, INFγ, Eomesodermin (Eomes), and lower levels of BCL2L11, maintained higher levels of phosphorylated AKT, and displayed enhanced sensitivity to the proliferative and anti-apoptotic effects of γ-chain cytokines compared to CTLs derived from TN/SCM. Higher frequencies of CTLs derived from TCM retained CD28 expression and upon activation secreted higher levels of IL-2. In NOD/Scid IL-2RγCnull mice, CD8+ TCM derived CTLs engrafted to higher frequencies in response to human IL-15 and mounted robust proliferative responses to an immunostimulatory vaccine. Similarly, CD8+ TCM derived CD19CAR+ CTLs exhibited superior antitumor potency following adoptive transfer compared to their CD8+ TN/SCM derived counterparts. These studies support the use of TCM enriched cell products for adoptive therapy of cancer.

U2 - 10.1080/2162402X.2015.1072671

DO - 10.1080/2162402X.2015.1072671

M3 - SCORING: Journal article

C2 - 26942092

VL - 5

SP - e1072671

JO - ONCOIMMUNOLOGY

JF - ONCOIMMUNOLOGY

SN - 2162-402X

IS - 1

ER -