类有机物
癌症研究
离体
免疫系统
食管癌
癌症
食管
免疫检查点
CD8型
生物
免疫疗法
医学
体内
免疫学
内科学
细胞生物学
生物技术
作者
Yimei Jiang,Hua Zhao,Shuai Kong,Dan Zhou,Jin-Xiu Dong,Yulan Cheng,Shuo Zhang,Fei Wang,Andrew Kalra,Ning Yang,Dandan Wei,Jian Chen,Yuan‐Wei Zhang,De–Chen Lin,Stephen J. Meltzer,Yanyi Jiang
摘要
ABSTRACT Organoid culture systems are very powerful models that recapitulate in vivo organ development and disease pathogenesis, offering great promise in basic research, drug screening and precision medicine. However, the application of organoids derived from patients with cancer to immunotherapeutic research is a relatively untapped area. Esophageal cancer is one of the most lethal malignancies worldwide, including two major pathological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. ESCC shares many biological and genomic features with oral squamous cell cancers. Herein, we provide a versatile protocol for the establishment and maintenance of oral and esophageal organoid cultures derived from both murine and human samples. We describe culture conditions for organoids derived from normal tongue, esophagus and gastroesophageal junction, esophageal cancer and Barrett's esophagus. In addition, we establish an ex vivo model by co-culturing patient tumor-derived organoids and autologous CD8+ T lymphocytes to assess CD8+ T cell-mediated tumor killing. Our protocol can also be modified for organoid establishment from other squamous epithelia and carcinomas. The co-culture model can serve as a template for studies of other tumor-immune cell interactions and the efficacy of immune checkpoint blockade therapy.
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