Modelling immune cytotoxicity for cholangiocarcinoma with tumour-derived organoids and effector T cells

Zidi

et al. 2023

Cells

Spheroids and organoids are important novel players in medical and life science research. They are gradually replacing two-dimensional (2D) cell cultures. Indeed, three-dimensional (3D) cultures are closer to the in vivo reality and open promising perspectives for academic research, drug screening, and personalized medicine. A large variety of cells and tissues, including tumor cells, can be the starting material for the generation of 3D cultures, including primary tissues, stem cells, or cell lines. A panoply of methods has been developed to generate 3D structures, including spontaneous or forced cell aggregation, air–liquid interface conditions, low cell attachment supports, magnetic levitation, and scaffold-based technologies. The choice of the most appropriate method depends on (i) the origin of the tissue, (ii) the presence or absence of a disease, and (iii) the intended application. This review summarizes methods and approaches for the generation of cancer spheroids and organoids, including their advantages and limitations. We also highlight some of the challenges and unresolved issues in the field of cancer spheroids and organoids, and discuss possible therapeutic applications.

Section: Methodological Options In Front Of Research On Anticancer Th...mentioning

confidence: 99%

Cancer Spheroids and Organoids as Novel Tools for Research and Therapy: State of the Art and Challenges to Guide Precision Medicine

Zidi

et al. 2023

Cells

Clinical Translational Sci

“…established a 3D co‐culture system consisting of patient‐derived cholangiocarcinoma organoids and immune cells (such as PBMCs or purified T cells) and studied organoid cell death caused by PBMCs and purified T cells. Distinct responses of different PDOs to direct and indirect contact with immune cells were noted 103 . These results indicate that CIVMs with immune cells is technologically feasible and has great applications in assessing specific reactions to immunotherapies in vitro.…”

Section: Application Of Civms In Drug Development and Precision Medicinementioning

confidence: 74%

Complex in vitro model: A transformative model in drug development and precision medicine

Wang,

Hu,

et al. 2024

In vitro and in vivo models play integral roles in preclinical drug research, evaluation, and precision medicine. In vitro models primarily involve research platforms based on cultured cells, typically in the form of two‐dimensional (2D) cell models. However, notable disparities exist between 2D cultured cells and in vivo cells across various aspects, rendering the former inadequate for replicating the physiologically relevant functions of human or animal organs and tissues. Consequently, these models failed to accurately reflect real‐life scenarios post‐drug administration. Complex in vitro models (CIVMs) refer to in vitro models that integrate a multicellular environment and a three‐dimensional (3D) structure using bio‐polymer or tissue‐derived matrices. These models seek to reconstruct the organ‐ or tissue‐specific characteristics of the extracellular microenvironment. The utilization of CIVMs allows for enhanced physiological correlation of cultured cells, thereby better mimicking in vivo conditions without ethical concerns associated with animal experimentation. Consequently, CIVMs have gained prominence in disease research and drug development. This review aimed to comprehensively examine and analyze the various types, manufacturing techniques, and applications of CIVM in the domains of drug discovery, drug development, and precision medicine. The objective of this study was to provide a comprehensive understanding of the progress made in CIVMs and their potential future use in these fields.

“…This 3D co-culture induced tumor-specific T cell reactions that killed tumor organoids while sparing healthy organoids. The same approaches were carried out with cholangiocarcinoma organoids, with similar results [ 110 ]. Moreover, patient-derived organoids grown with an air–liquid interface, demonstrated preservation of the native infiltrated immune cells, as evidenced by the remarkable similarity in the T-cell receptor repertoire between the original tumors and their paired organoids [ 111 ].…”

Section: Future Is Coming Giving a New Dimension To The Tradementioning

confidence: 84%

A Bloody Conspiracy— Blood Vessels and Immune Cells in the Tumor Microenvironment

Terrassoux

Claux

Bacari

et al. 2022

Cancers

Cancer progression occurs in concomitance with a profound remodeling of the cellular microenvironment. Far from being a mere passive event, the re-orchestration of interactions between the various cell types surrounding tumors highly contributes to the progression of the latter. Tumors notably recruit and stimulate the sprouting of new blood vessels through a process called neo-angiogenesis. Beyond helping the tumor cope with an increased metabolic demand associated with rapid growth, this also controls the metastatic dissemination of cancer cells and the infiltration of immune cells in the tumor microenvironment. To decipher this critical interplay for the clinical progression of tumors, the research community has developed several valuable models in the last decades. This review offers an overview of the various instrumental solutions currently available, including microfluidic chips, co-culture models, and the recent rise of organoids. We highlight the advantages of each technique and the specific questions they can address to better understand the tumor immuno-angiogenic ecosystem. Finally, we discuss this development field’s fundamental and applied perspectives.