2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.52

PP01.52 - Jun Zhang

Pdf Summary

The study presented at the 2024 Asia Conference on Lung Cancer explored the impact of Bifidobacteria-derived extracellular vesicles (Bif.BEVs) on the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC). ICIs, particularly anti-PD-1 and anti-PD-L1 agents, have dramatically changed NSCLC treatment, but not all patients benefit due to different forms of resistance. Previous research suggests that gut microbiota, especially the commensal Bifidobacterium, supports antitumor immunity and boosts ICI responses.<br /><br />In this study, Bif.BEVs were cultivated and isolated through rigorous methods and tested on both murine models and patient-derived lung cancer organoids. Bif.BEVs were found to significantly boost the therapeutic effects of anti-PD-1 agents by entering lung cancer cells and enhancing PD-L1 expression via the TLR4-NF-κB pathway. This process also included increasing important immune markers like IFN-γ and IL-2, boosting tumor-infiltrating CD8 T cells, and influencing multiple immune pathways.<br /><br />However, Bif.BEVs did not enhance the effects of anti-PD-L1 therapies to the same extent, likely due to the differential impact they have on the tumor immune microenvironment (TIME), such as upregulating PD-L2. This variation underscores the need for further research to fully understand these differential effects and how they might be leveraged for therapeutic advantage.<br /><br />The study suggests a novel mechanism by which gut microbiota can influence tumor immunity even in distant body sites, highlighting the potential for using Bif.BEVs to improve ICI therapies, particularly anti-PD-1 treatments. Researcher Jun Zhang disclosed associations with multiple pharmaceutical companies, which is typical for such studies and indicates significant engagement with the broader scientific and medical community.

Keywords

Bifidobacteria-derived extracellular vesicles

immune checkpoint inhibitors

non-small cell lung cancer

anti-PD-1 agents

gut microbiota

TLR4-NF-κB pathway

tumor immune microenvironment

tumor-infiltrating CD8 T cells

Bif.BEVs

Jun Zhang