Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice

Area of Science:

• Immunology
• Microbiology
• Oncology

Background:

• Gut microbiota plays a crucial role in maintaining immune homeostasis.
• Microbial dysbiosis is increasingly linked to altered tumor growth and therapeutic outcomes.

Purpose of the Study:

• To investigate the impact of gut microbiota disruption on melanoma tumorgenesis in a mouse model.
• To elucidate the underlying mechanisms by which gut microbiota influences tumor immune microenvironment and growth.

Main Methods:

• Utilized a mouse model of subcutaneous melanoma cell transplantation.
• Administered antibiotics to disrupt gut microbiota and assessed tumor growth and immune cell infiltration.
• Analyzed antigen-presenting cells (APCs), co-stimulatory molecules (CD80, CD86, MHCII), and Th1 cytokines (IFNγ, TNFα, IL12p40, IL12p35).
• Evaluated splenic APC function in T cell proliferation and IFNγ secretion.
• Administered lipopolysaccharide (LPS) to assess its effect on immune surveillance and tumor growth.

Main Results:

• Antibiotic-induced gut microbial dysbiosis promoted melanoma tumor growth.
• Dysbiosis led to reduced mature APC infiltration in tumors, decreased co-stimulatory molecule expression, and defective Th1 cytokine production.
• Splenic APCs showed impaired ability to stimulate T cell proliferation and IFNγ secretion in dysbiotic mice.
• Oral LPS administration restored immune surveillance and inhibited tumor growth in antibiotic-treated mice.

Conclusions:

• Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation and progression.
• Lipopolysaccharide (LPS) supplementation can restore effective immune surveillance and suppress tumor initiation in the context of microbial dysbiosis.