Microorganisms in cancer tertiary lymphoid structure formation.

Area of Science:

• Immunology
• Oncology
• Microbiology

Background:

• Tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) that significantly enhance the effectiveness of immune checkpoint blockade (ICB) therapy.
• The presence of TLSs is a strong predictive biomarker for ICB therapy response in various cancers.
• Emerging evidence highlights the role of diverse microorganisms (bacteria, viruses, fungi) in modulating ICB treatment outcomes.

Purpose of the Study:

• This review aims to elucidate the intricate relationship between microorganisms and TLS formation within the TME.
• It focuses on the signaling pathways involved in TLS development and how microbial interactions influence these pathways.
• The review seeks to identify potential diagnostic and therapeutic targets based on these microbial-TLS interactions.

Main Methods:

• This review synthesizes current research on TLS formation mechanisms, including key signaling pathways.
• It analyzes studies investigating the impact of various microorganisms on TLS development.
• The review discusses how microbes affect chemokines, antigen presentation, and immune cell function in the context of TLS formation.

Main Results:

• Microorganisms play a significant role in facilitating TLS formation by influencing critical signaling pathways.
• Specific microbial species can modulate the TME, impacting immune cell infiltration and function necessary for TLS development.
• These microbial-driven changes in TLSs are linked to altered responses to ICB therapy.

Conclusions:

• Understanding the mechanisms by which microorganisms influence TLS formation is crucial for advancing cancer immunotherapy.
• Microorganisms, chemokines, and signaling pathways involved in TLS development represent promising biomarkers for predicting ICB efficacy.
• Targeting microbial-T LS interactions could lead to novel therapeutic strategies to improve cancer treatment outcomes.