Abstract
Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. T cells then exert a targeted response throughout the body at areas not subjected to RT. These effects are further augmented through the use of immunotherapeutic drugs resulting in increased T-cell activity. Tumor-infiltrating lymphocyte presence and TREX1, KPNA2 and p53 signal expression are being explored as prognostic biomarkers.
Keywords:
abscopal effect; autologous tumor vaccine; immunotherapy; radiation therapy/radiotherapy; vaccines.
MeSH terms
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Biomarkers, Tumor / analysis
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Biomarkers, Tumor / metabolism
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Cell Movement / radiation effects
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Chemoradiotherapy / methods*
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Clinical Trials as Topic
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DNA Damage / immunology
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DNA Damage / radiation effects
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Dendritic Cells / immunology*
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Dendritic Cells / radiation effects
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Exodeoxyribonucleases / analysis
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Exodeoxyribonucleases / metabolism
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Humans
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Immune Checkpoint Inhibitors / pharmacology
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Immune Checkpoint Inhibitors / therapeutic use*
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Lymphocytes, Tumor-Infiltrating / drug effects
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / metabolism
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Lymphocytes, Tumor-Infiltrating / radiation effects
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / mortality
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Neoplasms / radiotherapy*
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Phosphoproteins / analysis
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Phosphoproteins / metabolism
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Prognosis
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Progression-Free Survival
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Radiotherapy Dosage
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / radiation effects
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / immunology
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Tumor Microenvironment / radiation effects
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Tumor Suppressor Protein p53 / analysis
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Tumor Suppressor Protein p53 / metabolism
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alpha Karyopherins / analysis
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alpha Karyopherins / metabolism
Substances
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Biomarkers, Tumor
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Immune Checkpoint Inhibitors
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KPNA2 protein, human
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Phosphoproteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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alpha Karyopherins
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Exodeoxyribonucleases
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three prime repair exonuclease 1