Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity

Area of Science:

• Immunology
• Cancer Research
• Innate Immunity

Background:

• Trained innate immunity enhances responses to secondary challenges.
• The potential of trained immunity in anti-tumor strategies is largely unexplored.
• Modulating myeloid cells or progenitors can induce trained immunity.

Purpose of the Study:

• To investigate if trained immunity can be induced to enhance anti-tumor immunity.
• To explore the mechanisms underlying β-glucan-induced anti-tumor effects.
• To determine the therapeutic potential of trained immunity in cancer.

Main Methods:

• Mice were pre-treated with β-glucan, a trained immunity agonist.
• Transcriptomic and epigenetic analyses were performed on myeloid cells.
• Neutrophils were adoptively transferred, and tumor growth was monitored.
• Bone marrow transplantation was used to assess transmissibility.

Main Results:

• β-glucan pre-treatment diminished tumor growth in mice.
• Trained immunity involved epigenetic and transcriptomic rewiring of granulopoiesis and neutrophil reprogramming.
• Type I interferon signaling was crucial for the anti-tumor effect, independent of adaptive immunity.
• Adoptive transfer of neutrophils from trained mice suppressed tumor growth via reactive oxygen species (ROS).
• The anti-tumor effect was transmissible through bone marrow transplantation.

Conclusions:

• β-glucan-induced trained immunity demonstrates a novel anti-tumor effect.
• Reprogramming of granulopoiesis and neutrophils is a key mechanism.
• This approach offers a therapeutically relevant strategy for enhancing anti-tumor immunity.