2. Academic Validation
  3. LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer

LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer

  • Mol Cancer. 2024 Sep 2;23(1):184. doi: 10.1186/s12943-024-02099-4.
Bo Wu 1,  Xin Huang 2,  Xiang Shi 3,  Meixi Jiang 4,  Hongxu Liu 5,  Li Zhao 6
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, 110136, China.
  • 2 Department of General practice medicine, Shengjing Hospital of China Medical University, Shenyang, 110022, China.
  • 3 Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China.
  • 4 Department of Neurology, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
  • 5 Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China. hgjxlzdsb@163.com.
  • 6 Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, 110136, China. sjhxnhzl@163.com.
PMID: 39223601 DOI: 10.1186/s12943-024-02099-4
Abstract

Great progress has been made in utilizing Immune Checkpoint blockade (ICB) for the treatment of non-small-cell lung Cancer (NSCLC). Therapies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, expressed on tumor cells, have demonstrated potential in improving patient survival rates. An unresolved issue involves immune suppression induced by exosomal PD-L1 within the tumor microenvironment (TME), particularly regarding CD8+ T cells. Our study unveiled the crucial involvement of LAMTOR1 in suppressing the exosomes of PD-L1 and promoting CD8+ T cell infiltration in NSCLC. Through its interaction with HRS, LAMTOR1 facilitates PD-L1 lysosomal degradation, thereby reducing exosomal PD-L1 release. Notably, the ability of LAMTOR1 to promote PD-L1 lysosomal degradation relies on a specific ubiquitination site and an HRS binding sequence. The findings suggest that employing LAMTOR1 to construct Peptides could serve as a promising strategy for bolstering the efficacy of immunotherapy in NSCLC. The discovery and comprehension of how LAMTOR1 inhibits the release of exosomal PD-L1 offer insights into potential therapeutic strategies for improving immunotherapy. It is imperative to conduct further research and clinical trials to investigate the feasibility and efficacy of targeting LAMTOR1 in NSCLC treatment.

Keywords

Exosomes; Immunotherapy; LAMTOR1; Non-small cell lung cancer; PD-L1.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z