Wu, CatherineKeskin, DerinLiu, Min2021-07-2020212021-07-192021Liu, Min. 2021. Investigating the Impact of Chemotherapy Exposure on Peripheral Immune Responses for Patients with Ovarian Cancer. Master's thesis, Harvard Medical School.28498743https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368637The current treatment of epithelial ovarian cancer (EOC) is based on surgical tumor debulking and platin-based chemotherapy. Neoadjuvant chemotherapy is used for initial tumor shrinkage before debulking surgery, but potentially also improves anti-tumor immune responses. Although the exact mechanisms are still unclear, we hypothesized that chemotherapy would lead to enhanced T cell responses. To explore peripheral immune responses following chemotherapy, we tested the function of T cells from peripheral blood mononuclear cell (PBMC) samples over the course of chemotherapy using ELISPOT assays and evaluated the dynamics of T cell repertoire and immune cell composition changes using bulk and single-cell RNA sequencing. T cells showed improved response to viral antigens after chemotherapy which was more pronounced in patients who initially responded to chemotherapy. Furthermore, we observed a trend towards increased central memory CD8+ and regulatory T cells regardless of chemotherapy response, and higher T cell clonotype turnover in chemotherapy responders. Finally, chemotherapy led to increased frequencies of monocytes in peripheral blood with higher HLA class II expression. These findings are consistent with a model in which induction chemotherapy leads to disinhibition of T cell responses due to reduced tumor burden and decreased inhibitory signaling. This is additionally aided through increased antigen presentation by monocytes. In sum, we provide evidence of immune-modulatory properties of chemotherapy in EOC which should be followed up in future studies.application/pdfenImmunologyThesis or Dissertation2021-07-200000-0002-7253-076X