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Dynamic change of immune microenvironment in ovarian cancer following neoadjuvant chemotherapy

ABSTRACT: Dynamic change of immune microenvironment in ovarian cancer following neoadjuvant chemotherapy

PROVIDER: PRJNA1292875 | ENA |

REPOSITORIES: ENA

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Dynamic change of immune microenvironment in ovarian cancer following neoadjuvant chemotherapy

Project description:Initial surgery and platinum-based chemotherapy is extensively applied to ovarian cancer. Although the majority of patients were sensitive, most relapse at later stage, highlighting the urgent need to understand the tumor microenvironment in ovarian cancer following NACT (neoadjuvant chemotherapy). Through analyzing the published scRNA-seq on human high-grade serous ovarian cancer and performing several in vitro and in vivo experiments, we found prostaglandins-mediated immunosuppressive microenvironment formation is a critical contributor to chemotherapy-resistant upon cisplatin treatment. In mechanisms, cisplatin-treated ovarian cancer cells induce the formation of MDSCs, which passivates the cytotoxicity of CD8+T cell. Moreover, we also carried out scRNA-seq on mice ovarian cancer intraperitoneal injection model to confirm our findings. Notably, Collaborative application of cisplatin and prostaglandins-specific inhibition boosts the cytotoxicity of CD8+T cell and greatly improves the effective rate compared to cisplatin monotherapy.

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TMT-based Quantitative Proteomics Identifies Protein Markers of Resistance to Neoadjuvant Chemotherapy in Ovarian Cancer

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Project description:We explore the potential of immune-associated expression profiles in a series of Epithelial Ovarian Cancer (EOC) patients undergoing neoadjuvant chemotherapy (NACT), comparing primary lesions before patients underwent carboplatin/paclitaxel-based NACT (so-called ´biopsy samples´) and interval debulking surgery (IDS) samples from residual lesions after treatment with chemotherapy (so-called ´surgery samples´).

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Proteomic Alterations Associated with Residual Disease in Neoadjuvant Chemotherapy Treated Ovarian Cancer Tissues

Project description:Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome in the management of high-grade serous ovarian cancer (HGSOC) patients. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) offers an alternate approach to management of HGSOC patients to achieve complete resection. This study assessed proteomic alterations in matched, chemotherapy naïve and NACT-treated patients tumors obtained from HGSOC patients with suboptimal (R1) versus optimal (R0) debulking at IDS. We describe distinct proteome profiles in pre- and post-NACT HGSOC tumors correlating with residual disease status providing prognostic biomarkers for residual disease at IDS as well as candidate proteins associated with NACT resistance warranting further pre-clinical investigation.

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Project description:Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy.

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