Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design

在基于细胞的免疫疗法设计中,分析卵巢癌肿瘤及其微环境在疾病进展过程中的变化

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作者:Yan-Ruide Li ,Christopher J Ochoa ,Yichen Zhu ,Adam Kramer ,Matthew Wilson ,Ying Fang ,Yuning Chen ,Tanya Singh ,Gabriella Di Bernardo ,Enbo Zhu ,Derek Lee ,Neda A Moatamed ,Joanne Bando ,Jin J Zhou ,Sanaz Memarzadeh ,Lili Yang

Abstract

Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease.

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