Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy.

Autor:	Esser LK; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Branchi V; Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany., Leonardelli S; Medical Faculty, Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany., Pelusi N; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Simon AG; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Klümper N; Department of Urology, University Hospital Bonn, Bonn, Germany., Ellinger J; Department of Urology, University Hospital Bonn, Bonn, Germany., Hauser S; Department of Urology, University Hospital Bonn, Bonn, Germany., Gonzalez-Carmona MA; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany., Ritter M; Department of Urology, University Hospital Bonn, Bonn, Germany., Kristiansen G; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Schorle H; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Hölzel M; Medical Faculty, Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany., Toma MI; Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2020 Sep 22; Vol. 10, pp. 1775. Date of Electronic Publication: 2020 Sep 22 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.01775
Abstrakt:	Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer accounting for 80% of all renal cancers as well as the majority of renal cancer-associated deaths. During the last decade, the treatment paradigm for ccRCC has radically changed. In particular, the recent development of immune checkpoint inhibitors (ICI) has led to an increased overall survival in the metastatic setting. Moreover, novel immune therapies targeting the tumor microenvironment have been developed. In this rapidly evolving treatment landscape, precise tools for personalized cancer therapy are needed. Here, we collected fresh tissue from 42 patients who underwent surgical resection for renal cell carcinoma. Part of the tissue was used to obtain formalin-fixed, paraffin-embedded samples or RNA. The remaining tissue was minced and cultured in a collagen-based three-dimensional, air-liquid interface (ALI) culture system. The generated patient-derived tumor organoids (ALI PDOs) were characterized by immunohistochemistry staining and RNA sequencing to validate their close similarity to the matched tumor. Immune cells and stromal cells within the microenvironment could be identified. Finally, we treated 10 ALI PDOs with the commonly used targeted cancer drug cabozantinib or the ICI nivolumab. Interestingly, we observed varying responses of ALI PDOs to these treatments and future studies are needed to investigate whether the ALI PDO approach could inform about treatment responses in patients. In conclusion, this three-dimensional ccRCC culture model represents a promising, facile tool for monitoring tumor responses to different types of therapies in a controlled manner, yet, still preserves the key features of the tumor of origin. (Copyright © 2020 Esser, Branchi, Leonardelli, Pelusi, Simon, Klümper, Ellinger, Hauser, Gonzalez-Carmona, Ritter, Kristiansen, Schorle, Hölzel and Toma.)
Databáze:	MEDLINE
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