Search

In this Viewpoint article,Nature Reviews Immunologyasks five experts in the field to share their thoughts on the development and immune functions of plasmacytoid dendritic cells. Importantly, will these cells be a useful clinical target?

In this Viewpoint, six leading experts consider the ways in which the microbiota can influence immune responses to cancer. Immunotherapies have been revolutionary in the treatment of cancer, but will we one day further increase their efficacy with microbiota-derived drugs?

In this Viewpoint article, we asked four scientists working on the cancer microbiome to provide their opinions on the current state of the field, where the research is heading and the challenges of implementing this field for clinical utility.

The authors of some of our most popular Reviews look back on a decade of immunology.

Integrated analysis of microbiome and host cell transcriptional data on clinically annotated cohorts of patients with melanoma who were treated with anti-programmed cell death protein-1, uncovers new associations of streptococcus species with immune-related adverse effects and finds consistent microbiome associations with clinical outcomes.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.

The human microbiota influences a whole range of physiological functions. In this Review, Roy and Trinchieri discuss our current understanding of how the gut microbiota modulates responses to cancer therapy as well as mediating susceptibility to toxic side effects.

The ability of NKG2D to trigger costimulation in CD8⁺ T cells and cytotoxicity in NK cells is thought to arise from its differential association with the intracellular signaling molecules DAP10 and DAP12, respectively. This model has now been refined to include the ability of DAP10 to mediate cytotoxic signals.

Four new papers focused on how interleukin 10–producing cells are induced have led to some unexpected and intriguing observations on the nature of interleukin 17–producing T helper cells.

Dendritic cell subsets are thought to become committed to the dendritic cell lineage once they have differentiated from lymphoid or myeloid lineage precursors. However, this tenet has been challenged by data showing plasticity among the different subsets.

Plasmacytoid dendritic cells express the microRNA miR-126, which controls their survival and effector functions via the receptor VEGFR2.

DAP12-coupled receptors influence signals emanating from Toll-like receptors, integrins and receptors for cytokines and growth factors. New findings indicate that DAP12 also facilitates the ability of CSF-1R, the receptor for M-CSF, to induce the stabilization and nuclear translocation of β-catenin.

Recent evidence indicates that the intestinal microbiota has important functions in maintaining intestinal homeostasis through crosstalk with the innate immune system. However, changes in the intestinal microbiota or breakdown of this crosstalk can result in colitis and colitis-associated colorectal cancer.

The gut microbiota has been shown to regulate responses to various cancer therapies, and the microbial species involved and their underlying mechanisms have begun to be unravelled. In this Perspective, Fernandes and colleagues present this evidence and then outline how it could be used to develop microbiota-based therapies for patients with cancer.

Western diet is one of the major causes underlying diabetes, and the microbes residing in the gut playing a critical role in mediating the effects of diet. Here the authors utilize network analysis to discover two species of Lactobacilli decreased by western diet, which improve glucose metabolism and restore of hepatic mitochondria in mice.

The cytokine like protein FAM3D (Fam3D in mice) is highly expressed in the digestive tract with unknown role in colon pathophysiology. Here, by using gene deficient mice, the authors show that Fam3D is critically involved in colon homeostasis, host defense against colitis-associated carcinogenesis, and the balance of microbiota.

Hild et al. find that a wild-derived microbiome protects against weight gain through early postnatal metabolic programming and brown adipose tissue activation.

CD4⁺ T cells contain a T-bet^high memory-phenotype (MP) population with innate-like functions. Here the authors characterize the requirements for their differentiation at homeostasis and identify a function for IL-12 that is tonically produced by type 1 dendritic cells in an MyD88- and CD40-dependent, but foreign PAMP-independent manner.

Bacteria within tumours affect progression and response to therapy; in addition, bacterial DNA can be detected in cell-free plasma. Herein, we discuss evidence showing that intratumoural bacteria are characteristic for each tumour type, and that detection of cell-free bacterial DNA in blood could provide an accurate and non-invasive test for cancer diagnosis.

The approval of anti-TNF therapy for colitis over 20 years ago represented a paradigm shift for the treatment of this disease. Anti-TNF therapy is now shown to prevent colitis-associated colon cancer in mice by modifying the gut microbiota composition and transcriptional activity, including genes in Escherichia coli that control colibactin synthesis.

Transkingdom Network Analysis (TkNA) is a unique analytical framework for inferring causal factors underlying host–microbiota and other multi-omic interactions, by integrating data from multiple cohorts and diverse omics types.

Emerging evidence indicates that the induction of an effective immune response involves the cooperation of multiple Toll-like receptors and other pattern-recognition receptors. Here, the role of this cooperation in host defence against various pathogens and the therapeutic implications are discussed.

In a mouse model of colorectal cancer, barrier deterioration results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives IL-23-dependent tumour growth.

Ultraviolet (UV) exposure has been implicated in melanoma formation. Here it is shown, in a mouse model, that UVB induces the recruitment of macrophages which produce interferon-γ to promote melanomagenesis. The study suggests that in melanomas, interferon-γ could be targeted therapeutically.

The ONCOBIOME network has generated new tools to measure dysbiosis and completed numerous trials aimed at modifying the microbiota to enhance cancer treatment; this Review summarizes the key advances and the progress toward translating them into clinical practice.

After the initial success of cancer immunotherapy using immune checkpoint blockers, the challenge is to understand why only a minority of patients respond to the therapy and to increase the rate of response. Three recent papers now report that the gut microbiota modulates the response to anti-PD1 therapy in patients with epithelial cancers or melanoma.