CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability
Copyright © 2021 Elsevier Inc. All rights reserved..
Understanding the mechanisms underlying how T cells become dysfunctional in a tumor microenvironment (TME) will greatly benefit cancer immunotherapy. We found that increased CD36 expression in tumor-infiltrating CD8+ T cells, which was induced by TME cholesterol, was associated with tumor progression and poor survival in human and murine cancers. Genetic ablation of Cd36 in effector CD8+ T cells exhibited increased cytotoxic cytokine production and enhanced tumor eradication. CD36 mediated uptake of fatty acids by tumor-infiltrating CD8+ T cells in TME, induced lipid peroxidation and ferroptosis, and led to reduced cytotoxic cytokine production and impaired antitumor ability. Blocking CD36 or inhibiting ferroptosis in CD8+ T cells effectively restored their antitumor activity and, more importantly, possessed greater antitumor efficacy in combination with anti-PD-1 antibodies. This study reveals a new mechanism of CD36 regulating the function of CD8+ effector T cells and therapeutic potential of targeting CD36 or inhibiting ferroptosis to restore T cell function.
| Errataetall: |
CommentIn: Cell Metab. 2021 Aug 3;33(8):1509-1511. - PMID 34348095 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Cell metabolism - 33(2021), 5 vom: 04. Mai, Seite 1001-1012.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Xingzhe [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.02.2022 Date Revised 06.05.2022 published: Print-Electronic CommentIn: Cell Metab. 2021 Aug 3;33(8):1509-1511. - PMID 34348095 Citation Status MEDLINE |
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| doi: |
10.1016/j.cmet.2021.02.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322481910 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a Understanding the mechanisms underlying how T cells become dysfunctional in a tumor microenvironment (TME) will greatly benefit cancer immunotherapy. We found that increased CD36 expression in tumor-infiltrating CD8+ T cells, which was induced by TME cholesterol, was associated with tumor progression and poor survival in human and murine cancers. Genetic ablation of Cd36 in effector CD8+ T cells exhibited increased cytotoxic cytokine production and enhanced tumor eradication. CD36 mediated uptake of fatty acids by tumor-infiltrating CD8+ T cells in TME, induced lipid peroxidation and ferroptosis, and led to reduced cytotoxic cytokine production and impaired antitumor ability. Blocking CD36 or inhibiting ferroptosis in CD8+ T cells effectively restored their antitumor activity and, more importantly, possessed greater antitumor efficacy in combination with anti-PD-1 antibodies. This study reveals a new mechanism of CD36 regulating the function of CD8+ effector T cells and therapeutic potential of targeting CD36 or inhibiting ferroptosis to restore T cell function | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a CD36 | |
| 650 | 4 | |a CD8(+) T cells | |
| 650 | 4 | |a ferroptosis | |
| 650 | 4 | |a lipid peroxidation | |
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| 650 | 7 | |a CD36 Antigens |2 NLM | |
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| 650 | 7 | |a Fatty Acids |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a spartalizumab |2 NLM | |
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| 700 | 1 | |a Liu, Lintao |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Lingqun |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Pan |e verfasserin |4 aut | |
| 700 | 1 | |a Bi, Enguang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Maojie |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Jianfei |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Qing |e verfasserin |4 aut | |
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