Consumption of β-glucans to spice up T cell treatment of tumors: a review

ABSTRACT

Introduction: Adoptive T-cell treatments of solid cancers have evolved into a robust therapy with objective response rates surpassing those of standardized treatments. Unfortunately, only a limited fraction of patients shows durable responses, which is considered to be due to a T cell-suppressive tumor microenvironment (TME). Here we argue that naturally occurring β-glucans can enable reversion of such T cell suppression by engaging innate immune cells and enhancing numbers and function of lymphocyte effectors.

Areas covered: This review summarizes timely reports with respect to absorption, trafficking and immune stimulatory effects of β-glucans, particularly in relation to innate immune cells. Furthermore, we list effects toward well-being and immune functions in healthy subjects as well as cancer patients treated with orally administered β-glucans, extended with effects of β-glucan treatments in mouse cancer models.

Expert opinion: Beta-glucans, when present in food and following uptake in the proximal gut, stimulate immune cells present in gut-associated lymphoid tissue and initiate highly conserved pro-inflammatory pathways. When tested in mouse cancer models, β-glucans result in better control of tumor growth and shift the TME toward a T cell-sensitive environment. Along these lines, we advocate that intake of β-glucans provides an accessible and immune-potentiating adjuvant when combined with adoptive T-cell treatments of cancer.

KEYWORDS:

• Adoptive T cell therapy
• β-glucans
• innate immunity
• pattern recognition receptors

Article highlights

• Orally ingested β-glucans are taken up in the proximal gut via intestinal epithelial cells or M-cells in Peyer’s patches, following which they are captured by subsets of CD103+ DCs and CXCR3+ macrophages within the GALT.

• Pro-inflammatory and T cell-enhancing effects such as diminishing T cell suppression by tumor-educated innate immune cells, and promoting T cell priming and Th1 differentiation have been attributed to β-glucans upon interaction with PRRs expressed by innate immune cells.

• Innate immune cells, following exposure to β-glucans, migrate to the bone marrow, spleen and lymph nodes where they support differentiation of effector lymphocytes, such as NK cells and CD8+ T cells.

• Amongst the β-glucans, those isolated from L. edodes and S. cerevisiae are the strongest biological and immunological modifiers according to clinical data with cancer patients and in vivo tumor mouse models.

• There is rationale to support adoptive T cell therapy with β-glucans derived from L. edodes and S. cerevisiae, not only because of T cell-potentiating abilities of these β-glucans but also because intake of β-glucans is safe, cheap, and enhances public health awareness.

• Chemistry, industrial production, and applications are currently not standardized and need to be better defined to select β-glucans as adjuvants.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.