Microbiota-induced T cell plasticity enables immune-mediated tumour control

Area of Science:

• Immunology
• Microbiome Research
• Cancer Therapy

Background:

• Immune checkpoint blockade (ICB) revolutionizes cancer care but has limited response rates.
• The gut microbiota influences immune function and response to cancer immunotherapy.
• Mechanisms by which gut bacteria affect ICB efficacy remain unclear.

Purpose of the Study:

• To investigate how colonization with segmented filamentous bacteria (SFB) impacts ICB efficacy.
• To elucidate the cellular mechanisms by which SFB influences anti-tumour immunity.

Main Methods:

• Utilized SFB colonization in mice with implanted SFB antigen-expressing melanoma.
• Employed T cell receptor (TCR) clonal lineage tracing, fate mapping, and MHC tetramer staining.
• Investigated the role of SFB-induced T helper 17 (T_H17) cells and their derivatives.

Main Results:

• Anti-programmed cell death protein 1 (PD-1) therapy was effective only in SFB-colonized mice.
• SFB induced antigen-specific T helper 1 (T_H1)-like cells derived from T_H17 cells in the gut.
• These T_H1-like cells promoted anti-tumour immunity by enhancing CD8+ T cell responses within the tumour microenvironment.

Conclusions:

• A single gut commensal (SFB) can imprint T cell plasticity, potentiating PD-1 blockade efficacy.
• SFB-induced T cell differentiation is crucial for anti-tumour immune responses and ICB effectiveness.
• Targeted microbiota modulation represents a potential strategy to improve ICB outcomes in cancer patients.