Targeting the Tumor Microenvironment in Radiation Oncology: Proceedings from the 2018 ASTRO–AACR Research Workshop | Clinical Cancer Research

12), and show decreased responsiveness to α-PD-1 therapiesnHighlight:Multiple studies have shown that response to immunotherapies are linked to the microbiota in patientsnHighlight:broad-spectrum antibiotic depletion of the microbiome results in radioresistance of cervical cancer to a single fraction of 6 GynHighlight:some of the absorbed SCFAs (e.g., the C4-SCFA, butyrate) have immunosuppressive effects in the TMEnHighlight:the microbiome is increasingly appreciated for its role in the processing of metabolites of microbial origin, and many of these byproducts (e.g., tryptophan metabolites) are immunosuppressive moleculesnHighlight:effective antitumor immunity is counter balanced by immune tolerance and immune suppression in the TMEnHighlight:antitumor immune responses after combined radiation and ICI depend on preexisting immunitynHighlight:metabolic changes in the TME affect the response to radiationnHighlight:hypoxia cause decreased mitochondrial function and increased lactate productionnHighlight:leads to hypoxia-inducible inhibitory phosphorylation of the pyruvate dehydrogenase E1α subunit, which enhances tumor growthnHighlight:hypoxia is not a problem of oxygen delivery, but rather is due to excessive oxygen consumption by tumors that cannot be met by supply demandsnHighlight:endocrine imbalances associated with obesity affect responsiveness to radiotherapynHighlight:glucose inhibitor 2-DG can sensitize these tumors to ionizing radiationnHighlight:caloric restriction led to radiosensitization of tumors in preclinical models and also suggested the potential of ketogenic diets, which are low in carbohydrates, to sensitize tumors to radiotherapynHighlight:cancer-associated fibroblasts secrete growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), FGF, and insulin-like growth factor 1nHighlight:radiation stimulates intratumoral infiltration of macrophages, with simultaneous induction of FGF2 and FGF receptor (FGFR)nHighlight:FGF signaling causes macrophages to switch from an M1 phenotype to an M2 phenotype, which mediate resistance to radiationnHighlight:intricate cross-talk between tumor-associated macrophages and mesenchymal stem cells (MSC) (30). M2-polarized macrophages educate MSCs to develop an M2 phenotype themselvesnHighlight:M1 macrophages promote radiosensitivity of inflammatory breast cancer cells, but M2 macrophages induce radioresistance via IL4/IL13-mediated STAT6 phosphorylationnHighlight:loss of expression of Notch1 increases the expression of ECM proteins and the infiltration of macrophages (33), which echoes Dr. R. Muschel’s findings that there is cross-talk between fibroblasts and macrophagesnHighlight:The microbiome is increasingly appreciated for its role in the processing of metabolites of microbial origin such as bacteria-derived SCFA, and many of these byproducts (e.g., the C4-SCFA, butyrate) have immunosuppressive effects in the TMEn]]>

About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.


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