Cover Image, Volume 42, Issue 8

Ding, Yuming; Chen, Chaojia; Ma, Shuaiya; Xue, Song; Zhao, Fangcheng; Peng, Jiali; Dong, Haoqing; Ma, Chao; Li, Chunyang

doi:10.1002/cac2.12355

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“…NFAT Luciferase Assay: Jurkat-NFAT-Luc cells were constructed by lentiviral transfection of pLV-NFAT-RE-Luci containing a nuclear factor of activated T cells (NFAT) response element-driven luciferase reporter, as previously described. [53] Jurat-NFAT-Luc cells were stimulated with platebound anti-CD3 (1 μg ml −1 ) and anti-CD28 (3 μg ml −1 ) antibodies for 6 h in the presence of 15 microbial metabolites (10 μm) involved in antitumor effects or immune regulation (Table S1, Supporting Information). [54,55] Luciferase activity was measured using the Firefly Luciferase Reporter Gene Assay Kit according to the manufacturer's instructions (cat#RG005, Beyotime Inc., Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8⁺ T Cell Fitness for Antitumor Immunity

Ma,

Wu,

et al. 2024

Advanced Science

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According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell‐mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA‐mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA‐ERK1/2‐ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA‐treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.

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Section: Methodsmentioning

confidence: 99%

Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8⁺ T Cell Fitness for Antitumor Immunity

Ma,

Wu,

et al. 2024

Advanced Science

Self Cite

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Cover Image, Volume 42, Issue 8

Abstract: The cover image is based on the Correspondence Intrinsic PD‐L1 promotes antitumor activity of CD8+ cytotoxic T lymphocytes via in cis interaction with CD80 by Yuming Ding et al., https://doi.org/10.1002/cac2.12337.

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Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8⁺ T Cell Fitness for Antitumor Immunity

Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8⁺ T Cell Fitness for Antitumor Immunity

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Cover Image, Volume 42, Issue 8

Abstract: The cover image is based on the Correspondence Intrinsic PD‐L1 promotes antitumor activity of CD8+ cytotoxic T lymphocytes via in cis interaction with CD80 by Yuming Ding et al., https://doi.org/10.1002/cac2.12337.

Cited by 1 publication

References 0 publications

Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity

Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity

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Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8⁺ T Cell Fitness for Antitumor Immunity

Urolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8⁺ T Cell Fitness for Antitumor Immunity