Microbial-induced trained immunity for cancer immunotherapy

Area of Science:

• Immunology
• Oncology
• Microbiology

Background:

• Myeloid cells are key components of the tumor microenvironment, with dual roles in cancer progression and immune regulation.
• The tumor microenvironment (TME) often presents a barrier to effective cancer immunotherapy due to immunosuppressive myeloid cells.

Purpose of the Study:

• To review the role of myeloid cells in cancer.
• To explore microbial-induced trained immunity (TRIM) as a strategy to reprogram myeloid cells into an immunostimulatory, antitumor state.
• To examine how microbial ligands enhance anti-tumor responses and synergize with existing immunotherapies.

Main Methods:

• Review of preclinical and clinical evidence on microbial-induced trained immunity in cancer.
• Analysis of mechanisms by which microbial ligands reprogram myeloid progenitors and tissue-resident cells.
• Examination of TRIM's synergy with cancer immunotherapies like immune checkpoint inhibitors.

Main Results:

• Bacillus Calmette-Guérin reprograms hematopoietic stem and progenitor cells for sustained anticancer immunity.
• β-glucan-induced TRIM enhances granulopoiesis and neutrophil-mediated tumor killing.
• Microbial-induced TRIM reshapes the immunosuppressive TME and boosts adaptive immunity, synergizing with immunotherapies.

Conclusions:

• Microbial-induced TRIM offers a novel strategy to overcome myeloid-driven immunosuppression in cancer.
• Further research is needed to address challenges like microbial product characterization, biomarker development, and optimized delivery.
• Harnessing TRIM holds potential for developing more effective and durable cancer immunotherapies.