There’s a lot of evidence that suggests increasing the mutational burden by inhibiting DNA repair factors increases the efficacy of immunotherapy. One hypothesis is through cGAS-STING or via other mechanisms. Pathology suggests that low expression of mismatch repair proteins in the tumor indicates that immunotherapy would be beneficial, but the mechanism is not entirely clear. Propose two hypotheses to explain how defects in DNA repair factors (or inhibiting them) increases the efficacy of immunotherapy and how you would test them. The Role of DNA Repair Factors in Enhancing the Efficacy of Immunotherapy

Immunotherapy: The Role Of DNA Repair Factors In Enhancing the Efficacy

An increasing number of evidences linking DNA damage factor inhibition and immunotherapy efficacy has led to a deeper exploration of the causes. The increased effectiveness of immunotherapy may result from the disruption of the cGAS–STING pathway (Ma et. al., 2018,). Another hypothesis suggests that DNA repair factor defects or inhibitions, like mismatch repair proteins may cause an increase in DNA damage. This could then be detected by the immune system and allow for enhanced immunotherapy (Kumar, et al. 2020). These hypotheses could be tested by allowing tumor cells to be infected with various DNA repair proteins. Then, the immune system can evaluate the cell’s response to the immunotherapy. The tumor’s expression of mismatch repair proteins can also be evaluated and linked to immunotherapy effectiveness. These hypotheses can be further supported by further analyses of various DNA repair pathways, and their effects upon tumor antigens. The experiments can provide information about the roles of DNA repair genes in the effectiveness of immunotherapy. Cont….

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