Endogenous Glucocorticoid Signaling Regulates CD8+ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment

Nandini Acharya; Asaf Madi; Huiyuan Zhang; Max Klapholz; Giulia Escobar; Shai Dulberg; Elena Christian; Michelle Ferreira; Karen O. Dixon; Geoffrey Fell; Katherine Tooley; Davide Mangani; Junrong Xia; Meromit Singer; Marcus Bosenberg; Donna Neuberg; Orit Rozenblatt-Rosen; Aviv Regev; Vijay K. Kuchroo; Ana C. Anderson

doi:10.1016/j.immuni.2020.08.005

Endogenous Glucocorticoid Signaling Regulates CD8⁺ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment

Nandini Acharya, Asaf Madi, Huiyuan Zhang, Max Klapholz, Giulia Escobar, Shai Dulberg, Elena Christian, Michelle Ferreira, Karen O. Dixon, Geoffrey Fell, Katherine Tooley, Davide Mangani, Junrong Xia, Meromit Singer, Marcus Bosenberg, Donna Neuberg, Orit Rozenblatt-Rosen, Aviv Regev^*, Vijay K. Kuchroo^*, Ana C. Anderson^*

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

Abstract

Acharya et al. uncover a gradient of increasing glucocorticoid signaling from naïve to dysfunctional CD8⁺ tumor-infiltrating lymphocytes. This gradient regulates effector transition and development of dysfunction. Glucocorticoid is produced locally by tumor-associated monocyte-macrophage lineage cells, and presence of active glucocorticoid signaling associates with poor response to immune checkpoint blockade.

Original language	English
Pages (from-to)	658-671.e6
Journal	Immunity
Volume	53
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2020.08.005
State	Published - 15 Sep 2020

Keywords

CD8 T cell
Nr3c1
TCF-1
cancer
dysfunction
exhaustion
glucocorticoid
immune checkpoint blockade
steroid
tumor-associated macrophages

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2020.08.005

Cite this

Acharya, N., Madi, A., Zhang, H., Klapholz, M., Escobar, G., Dulberg, S., Christian, E., Ferreira, M., Dixon, K. O., Fell, G., Tooley, K., Mangani, D., Xia, J., Singer, M., Bosenberg, M., Neuberg, D., Rozenblatt-Rosen, O., Regev, A., Kuchroo, V. K., & Anderson, A. C. (2020). Endogenous Glucocorticoid Signaling Regulates CD8⁺ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment. Immunity, 53(3), 658-671.e6. https://doi.org/10.1016/j.immuni.2020.08.005

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title = "Endogenous Glucocorticoid Signaling Regulates CD8+ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment",

abstract = "Acharya et al. uncover a gradient of increasing glucocorticoid signaling from na{\"i}ve to dysfunctional CD8+ tumor-infiltrating lymphocytes. This gradient regulates effector transition and development of dysfunction. Glucocorticoid is produced locally by tumor-associated monocyte-macrophage lineage cells, and presence of active glucocorticoid signaling associates with poor response to immune checkpoint blockade.",

keywords = "CD8 T cell, Nr3c1, TCF-1, cancer, dysfunction, exhaustion, glucocorticoid, immune checkpoint blockade, steroid, tumor-associated macrophages",

author = "Nandini Acharya and Asaf Madi and Huiyuan Zhang and Max Klapholz and Giulia Escobar and Shai Dulberg and Elena Christian and Michelle Ferreira and Dixon, {Karen O.} and Geoffrey Fell and Katherine Tooley and Davide Mangani and Junrong Xia and Meromit Singer and Marcus Bosenberg and Donna Neuberg and Orit Rozenblatt-Rosen and Aviv Regev and Kuchroo, {Vijay K.} and Anderson, {Ana C.}",

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year = "2020",

month = sep,

day = "15",

doi = "10.1016/j.immuni.2020.08.005",

language = "אנגלית",

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Acharya, N, Madi, A, Zhang, H, Klapholz, M, Escobar, G, Dulberg, S, Christian, E, Ferreira, M, Dixon, KO, Fell, G, Tooley, K, Mangani, D, Xia, J, Singer, M, Bosenberg, M, Neuberg, D, Rozenblatt-Rosen, O, Regev, A, Kuchroo, VK & Anderson, AC 2020, 'Endogenous Glucocorticoid Signaling Regulates CD8⁺ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment', Immunity, vol. 53, no. 3, pp. 658-671.e6. https://doi.org/10.1016/j.immuni.2020.08.005

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AU - Madi, Asaf

AU - Zhang, Huiyuan

AU - Klapholz, Max

AU - Escobar, Giulia

AU - Dulberg, Shai

AU - Christian, Elena

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AU - Dixon, Karen O.

AU - Fell, Geoffrey

AU - Tooley, Katherine

AU - Mangani, Davide

AU - Xia, Junrong

AU - Singer, Meromit

AU - Bosenberg, Marcus

AU - Neuberg, Donna

AU - Rozenblatt-Rosen, Orit

AU - Regev, Aviv

AU - Kuchroo, Vijay K.

AU - Anderson, Ana C.

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