Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

12,,,,,]. It leads to the formation of hypoxianHighlight:Hypoxia is an important metabolic element in TME that affects cell plasticity and tumor heterogeneitynHighlight:cells of the immune system are recruited to the TME and undergo specific “reprogramming”nHighlight:TAMs are involved in angiogenesis, immunosuppression, matrix remodeling, invasiveness, and metastasisnHighlight:inhibition of differentiation and maturation of dendritic cells (DCs), NK cell cytotoxicity, inactivation of proapoptotic pathways, inhibition of antigen presentation, disorders in receptor signaling of T cells, and activation of negative co-stimulatory signals like CTLA-4 (cytotoxic T-lymphocyte-associated protein 4)/CD80 (or CD86) and PD-1 (programmed death 1)/PDL-1 (programmed death ligand 1)nHighlight:abscopal effect, defined as “an action at a distance from the irradiated volume but within the same organism”nHighlight:Paradoxically, some of the processes taking place in the TME that are involved in the stimulation of the immune system may also participate in the activation of immunosuppression and induction of radioresistancenHighlight:After irradiation, immunosuppressive pathways are activated in the tumor microenvironmentnHighlight:second cancers as “late effects” of RT appearnHighlight:immunosuppressive cells are involved, namely Tregs, tolerogenic and immunosuppressive DCs, TAMs, TANs, MDSCs, and a number of molecules such as transforming growth factor-β (TGF-β), adenosine, VEGF, CSF-1, and CCL2nHighlight:Within a few hours after irradiation, granulocyte–macrophage colony-stimulating factor (GMC-SF) stimulation occurs, which promotes the migration of MDSCs to the circulatory system and to inflammatory tissuenHighlight:Arg1nHighlight:Factors activated in the TME in respose to RT that contribute to tumor radioresistancenHighlight:Radiation injury strengthens the proinflammatory response within the TME and recruits stromal CAFs—fibroblasts that promote tumor growthnHighlight:The switch from angiogenesis to vasculogenesis is supported by the activation of the stromal-cell-derived factor-1 (SDF-1) receptor (CXCR4) and stabilization of HIF1 []. Vasculogenesis is the main mechanism for repairing the vessel network and re-growth of the tumor after RTnHighlight:Hypoxia is a key regulatory factor for tumor growth that plays a critical role in radioresistance []. It correlates with tumor recurrence and poor prognosis after RT []. Hypoxia increases radioresistance more than three timesnHighlight:Hypoxia induces HIF-1α-mediated cell survivalnHighlight:hypoxia recruits immune cells [], including TAMs with the M2 phenotypenHighlight:despite the increasing precision and effectiveness of RT, recurrences of the neoplastic disease occurnHighlight:Low doses slightly activate the antitumor response, without significant impact on the cancer blood vessels, which does not damage the entire tumor. High doses activate the antitumor immune response but also cause destruction, with huge regions of hypoxia that trigger renewal processes that lead to a regrowth of the tumor. In both cases, cancer may recur.nHighlight:TME plays a key role in this processnHighlight:The key is to understand that TME is a “game changer” in the RT fight against cancernSticky notes:Game change in thinking—change and not use radiationn]]>

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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