Decision letter for "Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice"

Vaccinations improve the mortality and morbidity rates associated with several infections through the generation of antigen-specific immune responses. Adjuvants are often used together with vaccines to improve immunogenicity. However, the immune responses induced by most on-going vaccines and adjuvants approved for human use vary in individuals; this is a limitation that must be overcome to improve vaccine efficacy. Several reports have indicated that the symbiotic bacteria, particularly the gut microbiota, impact vaccine-mediated antigen-specific immune responses and promote the induction of nonspecific responses via the “training” of innate immune cells. Therefore, the interaction between gut microbiota and innate immune cells should be considered to ensure the optimal immunogenicity of vaccines and adjuvants. In this review, we first introduce the current knowledge on the immunological mechanisms of vaccines and adjuvants. Subsequently, we discuss how the gut microbiota influences immunity and highlight the relationship between gut microbes and trained innate immunity, vaccines, and adjuvants. Understanding these complex interactions will provide insights into novel vaccine approaches centered on the gut microbiota.

Download Full-text

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression

Nature Communications ◽

10.1038/s41467-020-18569-4 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Astrid De Boeck ◽

Bo Young Ahn ◽

Charlotte D’Mello ◽

Xueqing Lun ◽

Shyam V. Menon ◽

...

Keyword(s):

Immune Cells ◽

Therapeutic Strategy ◽

Innate Immune ◽

Dual Function ◽

Innate Immune Cells ◽

Murine Models ◽

Human Glioma ◽

Durable Response ◽

Host Environment ◽

Glioma Growth

Abstract Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.

Download Full-text