Role of Myeloid-Derived Suppressor Cells in Recurrent and Radiation Resistant Head and Neck Cancer
Mentor 1
Heather Himburg
Start Date
28-4-2023 12:00 AM
Description
Head and neck cancer (HNC) has an extremely high rate of recurrence and resistance to radiation therapy (RT). Due to this, the 5-year survival rate is below 50% for those suffering from locoregionally advanced disease. One factor believed to contribute to RT resistance and disease recurrence is the presence of myeloid-derived suppressor cells (MDSC). These are immature myeloid cells interrupted during the early phases of differentiation that have been shown to be present in greater amounts in samples taken from RT resistant patient tumors in comparison to treatment naïve samples. Additionally, MDSCs are known to increase cancer cell invasiveness and proliferation through the secretion of immunosuppressive cytokines which serve to further increase the recruitment of MDSCs to the tumor--resulting in decreased response to treatment and greater likelihood of recurrence. Thus, the role of MDSCs in RT resistance and disease recurrence in HNC will be investigated via the following methods. Primary patient tumor samples will be obtained using an IRB-approved protocol by surgical oncologist Dr. Zenga during surgery and evaluated via RT-PCR for long term changes to the tumor microenvironment (TME), comparing RT resistant to treatment naïve samples. MDSCs will be separated from the patient tumor samples using FACS sorting and exposed to RT ex vivo to identify the effects of RT on the isolated MDSC population. After treatment, RNA-Seq will be used to analyze transcriptional changes caused by RT in MDSCs independent of the tumor population. Finally, acute changes in the TME will be identified through observation of HNC cell lines derived from patient samples in response to ex vivo irradiation to aid in determining their role in RT resistance. PCR analysis following treatment of these cell lines will help identify changes in production of MDSC recruitment factors in the tumor population.
Role of Myeloid-Derived Suppressor Cells in Recurrent and Radiation Resistant Head and Neck Cancer
Head and neck cancer (HNC) has an extremely high rate of recurrence and resistance to radiation therapy (RT). Due to this, the 5-year survival rate is below 50% for those suffering from locoregionally advanced disease. One factor believed to contribute to RT resistance and disease recurrence is the presence of myeloid-derived suppressor cells (MDSC). These are immature myeloid cells interrupted during the early phases of differentiation that have been shown to be present in greater amounts in samples taken from RT resistant patient tumors in comparison to treatment naïve samples. Additionally, MDSCs are known to increase cancer cell invasiveness and proliferation through the secretion of immunosuppressive cytokines which serve to further increase the recruitment of MDSCs to the tumor--resulting in decreased response to treatment and greater likelihood of recurrence. Thus, the role of MDSCs in RT resistance and disease recurrence in HNC will be investigated via the following methods. Primary patient tumor samples will be obtained using an IRB-approved protocol by surgical oncologist Dr. Zenga during surgery and evaluated via RT-PCR for long term changes to the tumor microenvironment (TME), comparing RT resistant to treatment naïve samples. MDSCs will be separated from the patient tumor samples using FACS sorting and exposed to RT ex vivo to identify the effects of RT on the isolated MDSC population. After treatment, RNA-Seq will be used to analyze transcriptional changes caused by RT in MDSCs independent of the tumor population. Finally, acute changes in the TME will be identified through observation of HNC cell lines derived from patient samples in response to ex vivo irradiation to aid in determining their role in RT resistance. PCR analysis following treatment of these cell lines will help identify changes in production of MDSC recruitment factors in the tumor population.
