Recent advances in patient-derived tumor organoids for reconstructing TME of head and neck cancer.

The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient-derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine. We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient-derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions. In tumor development, the interaction between cellular and non-cellular components in the tumor microenvironment (TME) has a crucial role. Co-culture, Air-liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis. An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.

Chen L ，Chen Y ，Ge L ，Zhang Q ，Meng J ... -  《-》

ORGAVADS: establishment of tumor organoids from head and neck squamous cell carcinoma to assess their response to innovative therapies.

Radiotherapy is one of the cornerstones of the treatment of Head and Neck Squamous Cell Carcinomas (HNSCC). However, radioresistance is associated with a high risk of recurrence. To propose strategies (such as combinations with drugs) that could over intrinsic radioresistance, it is crucial to predict the response to treatment. Patient-Derived Tumor Organoids (PDTO) are in vitro tridimensional microtumors obtained from patient' own cancer samples. They have been shown to serve as reliable surrogates of the tumor response in patients. The ORGAVADS study is a multicenter observational trial conducted to investigate the feasibility of generating and testing PDTO derived from HNSCC for the evaluation of sensitivity to treatments. PDTO are obtained after dissociation of resected tumors remaining from tissues necessary for the diagnosis. Embedding of tumor cells is then performed in extracellular matrix and culture in medium supplemented with growth factors and inhibitors. Histological and immunohistochemical characterizations are performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovating combinations are assessed, as well as response to immunotherapy using co-cultures of PDTO with autologous immune cells collected from patient blood samples. Transcriptomic and genetic analyses of PDTO allow validation of the models compared to patients' own tumor and identification of potential predictive biomarkers. This study is designed to develop PDTO models from HNSCC. It will allow comparing the response of PDTO to treatment and the clinical response of the patients from whom they are derived. Our aim is to study the PDTO ability to predict the clinical response to treatment for each patient in view of a personalized medicine as well as to establish a collection of HNSCC models that will be useful for future innovative strategies evaluation. NCT04261192, registered February 7, 2020, last amendment v4 accepted on June, 2021.

Perréard M ，Florent R ，Divoux J ，Grellard JM ，Lequesne J ，Briand M ，Clarisse B ，Rousseau N ，Lebreton E ，Dubois B ，Harter V ，Lasne-Cardon A ，Drouet J ，Johnson A ，Le Page AL ，Bazille C ，Jeanne C ，Figeac M ，Goardon N ，Vaur D ，Micault E ，Humbert M ，Thariat J ，Babin E ，Poulain L ，Weiswald LB ，Bastit V ... -  《BMC CANCER》

Reconstructing the tumor architecture into organoids.

Cancer remains a leading health burden worldwide. One of the challenges hindering cancer therapy development is the substantial discrepancies between the existing cancer models and the tumor microenvironment (TME) of human patients. Constructing tumor organoids represents an emerging approach to recapitulate the pathophysiological features of the TME in vitro. Over the past decade, various approaches have been demonstrated to engineer tumor organoids as in vitro cancer models, such as incorporating multiple cellular populations, reconstructing biophysical and chemical traits, and even recapitulating structural features. In this review, we focus on engineering approaches for building tumor organoids, including biomaterial-based, microfabrication-assisted, and synthetic biology-facilitated strategies. Furthermore, we summarize the applications of engineered tumor organoids in basic cancer research, cancer drug discovery, and personalized medicine. We also discuss the challenges and future opportunities in using tumor organoids for broader applications.

Luo Z ，Zhou X ，Mandal K ，He N ，Wennerberg W ，Qu M ，Jiang X ，Sun W ，Khademhosseini A ... -  《-》

Exploring Tumor-Immune Interactions in Co-Culture Models of T Cells and Tumor Organoids Derived from Patients.

Jeong SR ，Kang M 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Liver organoids: a promising three-dimensional model for insights and innovations in tumor progression and precision medicine of liver cancer.

Primary liver cancer (PLC) is one type of cancer with high incidence rate and high mortality rate in the worldwide. Systemic therapy is the major treatment for PLC, including surgical resection, immunotherapy and targeted therapy. However, mainly due to the heterogeneity of tumors, responses to the above drug therapy differ from person to person, indicating the urgent needs for personalized treatment for PLC. Organoids are 3D models derived from adult liver tissues or pluripotent stem cells. Based on the ability to recapitulate the genetic and functional features of in vivo tissues, organoids have assisted biomedical research to make tremendous progress in understanding disease origin, progression and treatment strategies since their invention and application. In liver cancer research, liver organoids contribute greatly to reflecting the heterogeneity of liver cancer and restoring tumor microenvironment (TME) by co-organizing tumor vasculature and stromal components in vitro. Therefore, they provide a promising platform for further investigation into the biology of liver cancer, drug screening and precision medicine for PLC. In this review, we discuss the recent advances of liver organoids in liver cancer, in terms of generation methods, application in precision medicine and TME modeling.

Chen Y ，Liu Y ，Chen S ，Zhang L ，Rao J ，Lu X ，Ma Y ... -  《Frontiers in Immunology》