Abstract:Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well-being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases and even neuropsychiatric disorders. Thus, an interaction of mi… Show more
“…Colitis‐associated intestinal cancer has served as a paradigm for the connection between inflammation and cancer . Signals originating from microbes and dysbiosis are key drivers of gastrointestinal tumorigenesis . IL‐1 is downstream of microbial sensing by epithelial cells or innate immunity cells.…”
Section: Mechanisms Of Il‐1‐driven Tumor Promotionmentioning
Inflammation is an important component of the tumor microenvironment. IL-1 is an inflammatory cytokine which plays a key role in carcinogenesis and tumor progression. IL-1 is subject to regulation by components of the IL-1 and IL-1 receptor (ILR) families. Negative regulators include a decoy receptor (IL-1R2), receptor antagonists (IL-1Ra), IL-1R8, and anti-inflammatory IL-37. IL-1 acts at different levels in tumor initiation and progression, including driving chronic non-resolving inflammation, tumor angiogenesis, activation of the IL-17 pathway, induction of myeloid-derived suppressor cells (MDSC) and macrophage recruitment, invasion and metastasis. Based on initial clinical results, the translation potential of IL-1 targeting deserves extensive analysis.
“…Colitis‐associated intestinal cancer has served as a paradigm for the connection between inflammation and cancer . Signals originating from microbes and dysbiosis are key drivers of gastrointestinal tumorigenesis . IL‐1 is downstream of microbial sensing by epithelial cells or innate immunity cells.…”
Section: Mechanisms Of Il‐1‐driven Tumor Promotionmentioning
Inflammation is an important component of the tumor microenvironment. IL-1 is an inflammatory cytokine which plays a key role in carcinogenesis and tumor progression. IL-1 is subject to regulation by components of the IL-1 and IL-1 receptor (ILR) families. Negative regulators include a decoy receptor (IL-1R2), receptor antagonists (IL-1Ra), IL-1R8, and anti-inflammatory IL-37. IL-1 acts at different levels in tumor initiation and progression, including driving chronic non-resolving inflammation, tumor angiogenesis, activation of the IL-17 pathway, induction of myeloid-derived suppressor cells (MDSC) and macrophage recruitment, invasion and metastasis. Based on initial clinical results, the translation potential of IL-1 targeting deserves extensive analysis.
“…The microbiota influences diverse functions including gut permeability and barrier function, vitamin synthesis, metabolism, neurologic activity, metabolism of pharmaceuticals, and inflammation and immunity (Thomas et al, 2017b). While characterization of microbiota has been hindered in previous decades by limitations in culture methods, targeted and shotgun high-throughput sequencing technologies have more recently revolutionized our understanding of microbial diversity at various body sites.…”
Fungi are increasingly being recognized as common members of the microbiomes found on nearly all mucosal surfaces, and interest is growing in understanding how these organisms may contribute to health and disease. In this review, we investigate recent developments in our understanding of the fungal microbiota or “mycobiota” including challenges faced in characterizing it, where these organisms are found, their diversity, and how they interact with host immunity. Growing evidence indicates that like the bacterial microbiota, the fungal microbiota is often altered in disease states, and increasingly studies are being designed to probe the functional consequences of such fungal dysbiosis on health and disease.
“…Recent clinical data indicates that indoximod
safely heightens the efficacy of anti-PD1 in melanoma patients [116], consistent with preclinical data [117], suggesting that mTORC1 restoration
may be a sufficient cause of the antitumor effects of IDO1 blockade [116]. D-amino acids are used for signaling
by gut bacteria and the potential interface of IDO1 with the gut microbiome is
intriguing to consider in light of D-Trp and its mimetic indoximod as possible
PAMP molecules [118, 119]. Further mechanistic investigations of indoximod
might yield important new therapeutic directions.…”
Section: Therapeutic Approaches To Block Ido Functionmentioning
We discuss how small molecule inhibitors of the tryptophan catabolic
enzyme indoleamine 2,3-dioxygenase (IDOi) represent a vanguard of new
immunometabolic adjuvants to safely enhance the efficacy of cancer
immunotherapy, radiotherapy or 'immunogenic' chemotherapy by leveraging
responses to tumor neoantigens. IDO activation in cancer supports inflammatory
processes that IDOi can re-program to help clear tumors by blunting tumor
neovascularization and restoring immunosurveillance. Studies of regulatory and
effector pathways illuminate IDO as an inflammatory modifier. Recent work
suggests that coordinate targeting of the Trp catabolic enzymes TDO and IDO2 may
also safely broaden efficacy. Understanding IDOi as adjuvants to turn
immunologically 'cold' tumors 'hot' can seed new concepts in how to improve the
efficacy of cancer therapy while limiting its collateral damage.
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