“In vitro” 3D models of tumor-immune system interaction

Hirt, Christian; Papadimitropoulos, Adam; Mele, Valentina; Muraro, Manuele Giuseppe; Mengus, Chantal; Iezzi, Giovanna; Terracciano, Luigi; Martin, Ivan; Spagnoli, Giulio C.

doi:10.1016/j.addr.2014.05.003

Cited by 81 publications

(75 citation statements)

References 129 publications

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“…Although the functional roles of IL-17 in the tumor microenvironment remain to be further elucidated, it has been reported to promote angiogenesis [224], cancer cell growth and survival [225]. While there are recent advances in in vitro culture models of cancer-immune interactions, particularly through inclusion of immune cells in various 3D model systems [226], the supplementation of such cytokines to the culture medium in vitro, both for traditional and emerging co-culture studies, could potentially yield more clinically relevant results.…”

Section: Co-cultures With Immune Cellsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

157

134

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The development of novel cancer therapeutics is often plagued by discrepancies between drug efficacies obtained in preclinical studies and outcomes of clinical trials. The inconsistencies can be attributed to a lack of clinical relevance of the cancer models used for drug testing. While commonly used in vitro culture systems are advantageous for addressing specific experimental questions, they are often gross, fidelity-lacking simplifications that largely ignore the heterogeneity of cancers as well as the complexity of the tumor microenvironment. Factors such as tumor architecture, interactions among cancer cells and between cancer and stromal cells, and an acidic tumor microenvironment are critical characteristics observed in patient-derived cancer xenograft models and in the clinic. By mimicking these crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic.

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Section: Co-cultures With Immune Cellsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

157

134

View full text Add to dashboard Cite

show abstract

“…Typically, the arrangement of the cells in 2D primary culture permits less cell—cell interaction and absent ECM secretion, with concomitant effects on gene and protein expression and cellular behavior [7, 8]. Therefore, a novel method of culturing tumor cells, three-dimensional (3D) culture, was introduced in the 1970s [9].…”

Section: Introductionmentioning

confidence: 99%

Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma

Bai

Yang

Fan

et al. 2015

J Exp Clin Cancer Res

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BackgroundThree-dimensional (3D) culture models are considered to recapitulate the cell microenvironment in solid tumors, including the extracellular matrix (ECM), cell-cell interactions, and signal transduction. These functions are highly correlated with cellular behaviors and contribute to resistances against chemo- and radio-therapies. However, the biochemical effects and mechanisms remain unknown in soft sarcoma. Therefore, we developed an in vitro 3D model of sarcoma to analyze the reasons of the chemo- and radio-resistance in therapies.MethodsFour soft sarcoma cell lines, HT1080, RD, SW872, and human osteosarcoma cell line 1 (HOSS1), a cell line established from a patient-derived xenograft, were applied to 3D culture and treated with growth factors in methylcellulose-containing medium. Spheroids were examined morphologically and by western blotting, RT-qPCR, and immunofluorescence staining to analyze cell adhesion, gap junctions, ECM genes, and related factors. Proliferation and colony formation assays were performed to assess chemo- and radio-resistances between 3D and two-dimensional (2D) cell cultures. Annexin V and Propidium Iodide staining was used to detect early apoptotic sarcoma cells treated with Doxorubicin, Gemcitabine, and Docetaxel in the 3D model.ResultsThe four soft sarcoma cell lines formed spheres in vitro by culture in modified condition medium. Compared with 2D cell culture, expression of ECM genes and proteins, including COL1A1, LOX, SED1, FN1, and LAMA4, was significantly increased in 3D culture. Analysis of cadherin and gap junction molecules showed significant changes in the gene and protein expression profiles under 3D conditions. These changes affected cell–cell communication and were mainly associated with biological processes such as cell proliferation and apoptosis related to chemo- and radio-resistances.ConclusionsOur findings revealed significant differences between 3D and 2D cell culture systems, and indicated that cellular responsiveness to external stress such as radiation and chemotherapeutics is influenced by differential expression of genes and proteins involved in regulation of the ECM, cell adhesion, and gap junction signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0175-0) contains supplementary material, which is available to authorized users.

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“…In vitro 2D studies of immune-cancer cell interactions were crucial for discovering and understanding tumor associated antigens (TAA)[46]. Later, in vitro 3D studies were used to investigate immune-cancer cell interactions, such as immune cell infiltration of tumor spheroids.…”

Section: Microfluidics: Modeling Immune-cancer Cell Interactionsmentioning

confidence: 99%

“…3C–D). For example, stromal cells such as cancer-associated fibroblasts should be included in future studies because of their critical role in modulating the immune response via the secretion of cytokines[46]. Similarly, organ-specific cells could be added, eventually leading to “body-on-a-chip” platforms, wherein multiple organs are mimicked in different compartments of a single microfluidic device and connected via channels, recapitulating the systemic nature of the metastatic process [66].…”

Section: Outlook For Future Microfluidic Applications In Immunotherapymentioning

confidence: 99%

Microfluidics: A New Tool for Modeling Cancer–Immune Interactions

et al. 2016

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In recognition of the enormous potential of immunotherapies against cancer, research into the interactions between tumor and immune cells has accelerated, leading to the recent FDA approval of several drugs that reduce cancer progression. Numerous cellular and molecular interactions have been identified by which immune cells can intervene in the metastatic cascade, leading to the development of several in vivo and in vitro model systems that can recapitulate these processes. Among these, microfluidic technologies hold many advantages in terms of their unique ability to capture the essential features of multiple cell type interactions in three-dimensions while allowing tight control of the microenvironment and real-time monitoring. Here, we review current assays and discuss the development of new microfluidic technologies for immunotherapy.

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“In vitro” 3D models of tumor-immune system interaction

Cited by 81 publications

References 129 publications

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma

Microfluidics: A New Tool for Modeling Cancer–Immune Interactions

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