Abstract
Beta-glucans, natural polysaccharides derived from oats and fungi, have emerged as potent immunomodulators with significant potential in cancer therapy. Recent research demonstrates that beta-glucans can enhance anti-tumor immune responses, particularly when combined with immune checkpoint inhibitors. This review explores the mechanisms by which beta-glucans modulate the tumor microenvironment, summarizes preclinical and clinical findings, and discusses their future role as adjuncts in cancer immunotherapy.
Introduction
Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, not all patients respond, and resistance remains a challenge. Beta-glucans, known for their immunostimulatory properties, are being investigated as adjuvants to improve the efficacy of ICIs and other cancer therapies.
Mechanisms of Action
Beta-glucans activate both innate and adaptive immune responses by:
- Stimulating macrophages, dendritic cells, neutrophils, and natural killer (NK) cells through pattern recognition receptors such as dectin-1 and CR3[4][7].
- Enhancing antigen presentation and promoting the infiltration of immune cells into the tumor microenvironment[5].
- Reducing the immunosuppressive effects of regulatory T cells and myeloid-derived suppressor cells, thereby shifting the tumor milieu toward a more pro-inflammatory, anti-tumor state[5][8].
- Potentiating antibody-dependent cellular cytotoxicity, especially when used with monoclonal antibodies and checkpoint inhibitors[6].
Preclinical and Clinical Evidence
- Preclinical Studies: Beta-glucans have shown efficacy in mouse models of colorectal, pancreatic, and gastric cancers, where they increased immune cell infiltration and prolonged survival when combined with ICIs[2][3][5][8].
- Clinical Trials: Early-phase clinical studies indicate that beta-glucan supplementation alongside ICIs and chemotherapy is safe and may improve response rates and survival in patients with advanced cancers, including gastric adenocarcinoma[5][6].
- Quality of Life: Beta-glucans have also been reported to mitigate chemotherapy-induced side effects, such as mucositis and leukopenia, enhancing patient quality of life[3].
Therapeutic Implications
The integration of beta-glucans with checkpoint inhibitors offers several advantages:
- Enhanced anti-tumor immunity and improved efficacy of ICIs[5][6].
- Reduced tumor recurrence and improved long-term survival in some cancer types[3].
- Favorable safety profile and natural origin, supporting their use as adjuncts in immunotherapy regimens[6].
Conclusion
Beta-glucans from oats and fungi represent a promising adjunct to checkpoint inhibitor therapy, capable of reprogramming the tumor microenvironment and enhancing anti-tumor immunity. Ongoing clinical trials and mechanistic studies will further clarify their role in cancer immunotherapy and may expand their application across multiple tumor types.
Keywords: beta-glucan, immunomodulation, checkpoint inhibitors, cancer immunotherapy, tumor microenvironment, anti-tumor immunity
Citations:
[1] Potential promising anticancer applications of β-glucans: a review https://pmc.ncbi.nlm.nih.gov/articles/PMC10776902/
[2] β-glucan: a potent adjuvant in immunotherapy for digestive tract … https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1424261/full
[3] β-glucan: a potent adjuvant in immunotherapy for digestive tract … https://pmc.ncbi.nlm.nih.gov/articles/PMC11294916/
[4] Beta glucan as an immune stimulant in tumor microenvironment https://www.sciencedirect.com/science/article/abs/pii/S014181302300510X
[5] An exploratory clinical study of β-glucan combined with … – Frontiers https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1448485/full
[6] β‑glucan vaccine adjuvant approach for cancer treatment through … https://www.spandidos-publications.com/10.3892/or.2021.8225
[7] The Effects of β-glucans on Cancer Metastasis | Bentham Science https://eurekaselect.com/public/article/51862
[8] A β-1,3/1,6-glucan enhances anti-tumor effects of PD1 antibody by … https://www.sciencedirect.com/science/article/abs/pii/S0141813024054655
