Gut commensal Bifidobacterium-derived extracellular vesicles modulate the therapeutic effects of anti-PD-1 in lung cancer

Ranjan Preet, Md Atiqul Islam, Jiyoung Shim, Ganeshkumar Rajendran, Amrita Mitra, Vikalp Vishwakarma, Caleb Kutz, Sonali Choudhury, Harsh Pathak, Qun Dai, Weijing Sun, Rashna Madan, Cuncong Zhong, Mary A. Markiewicz and Jun Zhang ()
Additional contact information
Ranjan Preet: University of Kansas Medical Center
Md Atiqul Islam: University of Kansas Medical Center
Jiyoung Shim: University of Kansas Medical Center
Ganeshkumar Rajendran: University of Kansas Medical Center
Amrita Mitra: University of Kansas Medical Center
Vikalp Vishwakarma: University of Kansas Medical Center
Caleb Kutz: University of Kansas Medical Center
Sonali Choudhury: University of Kansas Comprehensive Cancer Center
Harsh Pathak: University of Kansas Medical Center
Qun Dai: University of Kansas Medical Center
Weijing Sun: University of Kansas Medical Center
Rashna Madan: University of Kansas Medical Center
Cuncong Zhong: University of Kansas
Mary A. Markiewicz: University of Kansas Medical Center
Jun Zhang: University of Kansas Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Although immunotherapy such as anti-programmed death-1 and its ligand 1 (PD-1/L1) is a standard treatment for advanced non-small cell lung cancer (NSCLC), many patients do not derive benefit directly. Several studies have elucidated new strategies to improve the antitumor immune response through gut microbiota modulation. However, it remains largely debatable regarding how gut microbiota remotely affect lung cancer microenvironment and subsequently modulate immunotherapy response. Here we show that commensal Bifidobacterium-derived extracellular vesicles (Bif.BEVs) can modulate the therapeutic effect of anti-PD-1 therapy in NSCLC. These Bif.BEVs are up-taken by lung cancer cells predominantly via dynamin-dependent endocytosis and upregulate PD-L1 expression through TLR4-NF-κB pathway. They also efficiently penetrate murine intestinal and patient-derived lung cancer organoids. Oral gavage of these Bif.BEVs result in their accumulation in tumors in mice. Using a syngeneic mouse model, Bif.BEVs are found to synergize the anti-tumor effect of anti-PD-1 via modulation of key cytokines, immune response and oncogenic pathways, and increase in tumor-infiltrating CD8+ T cells. Our study therefore identifies a link between Bif.BEVs and the tumor microenvironment, providing an alternative mechanism to explain how gut microbiota can influence immunotherapy response, particularly in tumors located anatomically distant from the gut.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58553-4 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_s41467-025-58553-4

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

DOI: 10.1038/s41467-025-58553-4

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 ().