Investigating the Impact of Chemotherapy Exposure on Peripheral Immune Responses for Patients with Ovarian Cancer

Abstract

The 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.