CD137L promotes immune surveillance in melanoma via HLTF regulation

Long Liang, Lin Zhu, Xin Li, Wenbin Zhou, Yanbin Zhang, Mien-Chie Hung, Guanxiong Zhang (), Yong Chen (), Xinwei Kuang (), Juan Su (), Jing Liu (), Xiang Chen () and Hong Liu ()
Additional contact information
Long Liang: Central South University
Lin Zhu: Central South University
Xin Li: Central South University
Wenbin Zhou: Central South University
Yanbin Zhang: Central South University
Mien-Chie Hung: China Medical University
Guanxiong Zhang: Central South University
Yong Chen: Fudan University Shanghai Cancer Center
Xinwei Kuang: Central South University
Juan Su: Central South University
Jing Liu: Central South University
Xiang Chen: Central South University
Hong Liu: Central South University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Immune checkpoint blockers (ICBs) have demonstrated substantial efficacy across various malignancies, yet the benefits of ICBs are limited to a subset of patients. Therefore, it is essential to identify novel therapeutic targets. By integrating multi-omics data from cohorts of patients with melanoma treated with ICBs, a positive correlation is observed between tumor CD137L expression and the efficacy of PD-1 blockade. Functionally, CD137L induction in cancer cells significantly enhances anti-tumor immunity by promoting CD8+ T cell survival, both in vivo and in vitro. Mechanistically, helicase-like transcription factor (HLTF) is identified as a pivotal transcriptional regulator of CD137L, controlling its expression through phosphorylation of serine at position 398. Therapeutically, the AMPK agonist AICAR (acadesine) as an inducer of CD137L, exhibiting synergistic effects with PD-1 or CTLA-4 blockade. In summary, our findings elucidate a mechanism controlling CD137L expression and highlight a promising combination therapy to enhance the efficacy of ICBs in melanoma. One Sentence Summary: Inducing co-stimulatory immune checkpoint CD137L expression in melanoma cells enhances T cell-mediated anti-tumor immunity.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63338-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63338-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63338-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().