Precision-Cut Tumor Slices (PCTS) as an Ex Vivo Model in Immunotherapy Research

Dimou, Paraskevi; Trivedi, Sumita; Liousia, Maria; D'Souza, Reena R; Klampatsa, Astero

doi:10.3390/antib11020026

Cited by 11 publications

(8 citation statements)

References 61 publications

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“…PCTS are an ex vivo system that largely preserves the 3D tumor architecture, along with its TME and stroma. They are relatively easy to produce, and they can offer a platform for conducting therapy-based experiments on human solid tumor tissue 5 . However, our current understanding of the complex changes that occur during slice production and culture (even without any treatment-induced changers) is quite limited.…”

Section: Discussionmentioning

confidence: 99%

“…Although cell culture, murine models, and patient-derived xenografts provide key information about tumor cell biology, they are unable to replicate the complex human TME and extracellular matrix in a single model 1 – 3 . Precision cut tumor slices (PCTS), which are generated by cutting thin, viable cross sections of fresh tumors, offer a unique approach to study human solid tumors within an architecturally intact microenvironment where spatial relationships are left largely intact 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research

Trivedi,

Tilsed,

Liousia

et al. 2024

Sci Rep

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With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research

Trivedi,

Tilsed,

Liousia

et al. 2024

Sci Rep

Self Cite

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“…The other method is vibratome technology, which can generate slices from tens to hundreds of microns. Tissue slices generated by the vibratome are precisely cut to obtain a relatively regular shape, making them superior for culture and testing 46 . Therefore, the second method is most commonly used to generate tissue slices.…”

Section: Tissue Slicing Technology and Tissue Slicesmentioning

confidence: 99%

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

Wang,

Hu,

et al. 2024

Clinical Translational Sci

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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.

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“…This problem has been resolved through the development of newer tissue slicing technologies, such as tissue choppers, vibratomes (Vibratome), and compresstomes. [ 41 ] With these improved methods for tissue processing, tumor samples can be precisely cut into slices with a uniform thickness range of 30–1000 µm.…”

Section: Conventional Approaches For Maintaining Pde Culturesmentioning

confidence: 99%

Making In Vitro Tumor Models Whole Again

Adine

Mitriashkin

et al. 2023

Adv Healthcare Materials

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As a reductionist approach, patient‐derived in vitro tumor models are inherently still too simplistic for personalized drug testing as they do not capture many characteristics of the tumor microenvironment (TME), such as tumor architecture and stromal heterogeneity. This is especially problematic for assessing stromal‐targeting drugs such as immunotherapies in which the density and distribution of immune and other stromal cells determine drug efficacy. On the other end, in vivo models are typically costly, low‐throughput, and time‐consuming to establish. Ex vivo patient‐derived tumor explant (PDE) cultures involve the culture of resected tumor fragments that potentially retain the intact TME of the original tumor. Although developed decades ago, PDE cultures have not been widely adopted likely because of their low‐throughput and poor long‐term viability. However, with growing recognition of the importance of patient‐specific TME in mediating drug response, especially in the field of immune‐oncology, there is an urgent need to resurrect these holistic cultures. In this Review, the key limitations of patient‐derived tumor explant cultures are outlined and technologies that have been developed or could be employed to address these limitations are discussed. Engineered holistic tumor explant cultures may truly realize the concept of personalized medicine for cancer patients.

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Precision-Cut Tumor Slices (PCTS) as an Ex Vivo Model in Immunotherapy Research

Cited by 11 publications

References 61 publications

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research

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

Making In Vitro Tumor Models Whole Again

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