Cited by 1,033Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment

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Ma, Xingzhe, Bi, Enguang, Lu, Yong, Su, Pan, Huang, Chunjian, Liu, Lintao, Wang, Qiang, Yang, Maojie, Kalady, Matthew F., Qian, Jianfei, Zhang, Aijun, Gupte, Anisha A., Hamilton, Dale J., Zheng, Chengyun, Yi, Qing·2019·Cell Metabolism

DOI 10.1016/j.cmet.2019.04.002PMC PMC7061417

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Abstract

Tumor-infiltrating T cells often lose their effector function; however, the mechanisms are incompletely understood. We report that cholesterol in the tumor microenvironment induces CD8+ T cell expression of immune checkpoints and exhaustion. Tumor tissues enriched with cholesterol and cholesterol content in tumor-infiltrating CD8+ T cells were positively and progressively associated with upregulated T cell expression of PD-1, 2B4, TIM-3, and LAG-3. Adoptively transferred CD8+ T cells acquired cholesterol, expressed high levels of immune checkpoints, and became exhausted upon entering a tumor. Tumor culture supernatant or cholesterol induced immune checkpoint expression by increasing endoplasmic reticulum (ER) stress in CD8+ T cells. Consequently, the ER stress sensor XBP1 was activated and regulated PD-1 and 2B4 transcription. Inhibiting XBP1 or reducing cholesterol in CD8+ T cells effectively restored antitumor activity. This study reveals a mechanism underlying T cell exhaustion and suggests a new strategy for restoring T cell function by reducing cholesterol to enhance T cell-based immunotherapy.

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Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
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Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · cited 13×
“Tumor-infiltrating CD8+ T cells are associated with progressive loss of effector function due to prolonged antigen exposure and a suppressive tumor microenvironment (Wherry, 2011).”
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Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360 · cited 1×
“, the combination of anti-PD-1 with anti-CTLA-4 (Buchbinder and Desai, 2016; Duraiswamy et al., 2013; Dyck and Mills, 2017), anti-PD-1 with anti-TIM-3 (Sakuishi et al.”
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072
Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
Woo, S.-R., Turnis, M. E., Goldberg, M. V., Bankoti, J., Selby, M., Nirschl, C. J., Bettini, M. L., Gravano, D. M., Vogel, P., Liu, C. L., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-1620 · Cited by 1,647
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway
Boussiotis, V. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1514296 · Cited by 1,372
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Angelin, A., Gil‐de‐Gómez, L., Dahiya, S., Jiao, J., Guo, L., Levine, M. H., Wang, Z., Quinn, W. J., Kopinski, P. K., Wang, L., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.018 · Cited by 1,304
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors
Voron, T., Colussi, O., Marcheteau, E., Pernot, S., Nizard, M., Pointet, A.-L., Latreche, S., Bergaya, S., Benhamouda, N., Tanchot, C., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20140559 · Cited by 1,179
Statin use and reduced cancer-related mortality
Nielsen, S. F., Nordestgaard, B. G., & Bojesen, S. E. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1201735 · Cited by 1,030
Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism
Yang, W., Bai, Y., Xiong, Y., Zhang, J., Chen, S., Zheng, X., Meng, X., Li, L., Wang, J., Xu, C., et al. (2016) · Nature · doi:10.1038/nature17412 · Cited by 1,010

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Authors: Ma, X., Bi, E., Lu, Y., Su, P., Huang, C., Liu, L., Wang, Q., Yang, M., Kalady, M. F., Qian, J., Zhang, A., Gupte, A. A., Hamilton, D. J., Zheng, C., & Yi, Q.
Affiliations: Houston Methodist (US)
Wake Forest University Health Sciences (US)
Cleveland Clinic (US)
Houston Methodist Research Institute (US)
Second Hospital of Shandong University (CN)
Corresponding author: Yi, Qing
ORCID: Ma, Xingzhe
Bi, Enguang
Lu, Yong
Liu, Lintao
Wang, Qiang
Kalady, Matthew F.
Qian, Jianfei
Zhang, Aijun
Gupte, Anisha A.
Hamilton, Dale J.
Zheng, Chengyun
Yi, Qing
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2019-07
Volume: 30
Issue: 1
Pages: 143-156.e5
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2019.04.002
PMC: PMC7061417
OpenAlex: W2941036215
Cited by: 1,033
References: 45
Citations by year: 2026: 176 · 2025: 204 · 2024: 187 · 2023: 169 · 2022: 136 · 2021: 100 · 2020: 47 · 2019: 12
FWCI: 31.24
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: cholesterol, CD8+ T cell exhaustion, tumor microenvironment, immune checkpoint, PD-1, 2B4, TIM-3, LAG-3, endoplasmic reticulum stress, XBP1, adoptive T cell therapy, antitumor immunity, cholesterol metabolism
MeSH terms: Animals, Cholesterol, Flow Cytometry, Humans, Immunotherapy, Melanoma, Experimental, Blotting, Western, CD8-Positive T-Lymphocytes, Immunoprecipitation, Mice, Tumor Microenvironment, Real-Time Polymerase Chain Reaction, Programmed Cell Death 1 Receptor

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Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment

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