التفاصيل البيبلوغرافية
| العنوان: |
Exhaustion-associated cholesterol deficiency dampens the cytotoxic arm of antitumor immunity. |
| المؤلفون: |
Yan, Chengsong1,2 (AUTHOR), Zheng, Lin1,2 (AUTHOR), Jiang, Shutan1,2 (AUTHOR), Yang, Haochen1,2 (AUTHOR), Guo, Jun1,2 (AUTHOR), Jiang, Lu-yi3 (AUTHOR), Li, Tongzhou4 (AUTHOR), Zhang, Haosong4 (AUTHOR), Bai, Yibing2 (AUTHOR), Lou, Yu5 (AUTHOR), Zhang, Qi5 (AUTHOR), Liang, Tingbo5 (AUTHOR), Schamel, Wolfgang6 (AUTHOR), Wang, Haopeng7 (AUTHOR), Yang, Weiwei2 (AUTHOR), Wang, Guangchuan2 (AUTHOR), Zhu, Zheng-jiang4 (AUTHOR), Song, Bao-Liang1,3 (AUTHOR) blsong@whu.edu.cn, Xu, Chenqi1,2 (AUTHOR) cqxu@sibcb.ac.cn |
| المصدر: |
Cancer Cell. Jul2023, Vol. 41 Issue 7, p1276-1276. 1p. |
| مصطلحات موضوعية: |
*CYTOTOXIC T cells, *T cells, *T-cell exhaustion, *CHOLESTEROL, *CHOLESTEROL metabolism, *MYELOID cells |
| مستخلص: |
The concept of targeting cholesterol metabolism to treat cancer has been widely tested in clinics, but the benefits are modest, calling for a complete understanding of cholesterol metabolism in intratumoral cells. We analyze the cholesterol atlas in the tumor microenvironment and find that intratumoral T cells have cholesterol deficiency, while immunosuppressive myeloid cells and tumor cells display cholesterol abundance. Low cholesterol levels inhibit T cell proliferation and cause autophagy-mediated apoptosis, particularly for cytotoxic T cells. In the tumor microenvironment, oxysterols mediate reciprocal alterations in the LXR and SREBP2 pathways to cause cholesterol deficiency of T cells, subsequently leading to aberrant metabolic and signaling pathways that drive T cell exhaustion/dysfunction. LXRβ depletion in chimeric antigen receptor T (CAR-T) cells leads to improved antitumor function against solid tumors. Since T cell cholesterol metabolism and oxysterols are generally linked to other diseases, the new mechanism and cholesterol-normalization strategy might have potential applications elsewhere. [Display omitted] • Intratumoral T cells have cholesterol deficiency • CD8+ T cells are more vulnerable to cholesterol deficiency than CD4+ T cells • Cholesterol deficiency induces autophagy-mediated apoptosis of T cells • Oxysterols in the TME cause cholesterol deficiency of T cells by SREBP2/LXR alterations Yan et al. assess the cholesterol atlas of the tumor microenvironment and find that intratumoral T cells have cholesterol deficiency. Mechanistically, oxysterols alter SREBP2/LXR activities to cause cholesterol deficiency in T cells, thus affecting major metabolic and signaling pathways to reduce cell proliferation and to trigger autophagy-mediated apoptosis. [ABSTRACT FROM AUTHOR] |
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