Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment – New Findings and Future Perspectives

Nagl, Laurenz; Horvath, Lena; Pircher, Andreas; Wolf, Dominik

doi:10.3389/fcell.2020.00766

Cited by 126 publications

(118 citation statements)

References 186 publications

(369 reference statements)

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“…A growing body of evidence suggests that the ECs lining peritumoral vessels, termed Tumour Endothelial Cells (TECs), exhibit unique phenotypic and functional properties when compared to normal endothelial cells. They are highly proliferative and exhibit genetic instability and a stemness gene signature [ 93 ]. Furthermore, TECs not only promote tumour angiogenesis but also impact the immunogenic properties of the peritumoral niche.…”

Section: Cell–cell Communicationsmentioning

confidence: 99%

“…TECs can actively guide adhesion, rolling and extravasation of circulating immune cells into the tumour stroma, and impact T lymphocyte priming and migration [ 94 ]. In addition, TECs directly affect cancer progression and the formation of distant metastasis through angiocrine and paracrine signalling [ 93 ]. The leaky architecture of tumour vessels facilitates the hematogenous metastatic spread of cancer cells [ 95 ], and the adhesion molecules expressed by TECs act as scaffold directing malignant cells to intravasation [ 96 ].…”

Section: Cell–cell Communicationsmentioning

confidence: 99%

“…Similarly, the regulation of vascular niches is likely to be organ-specific. From this perspective, HUVECs derive from a rather unique tissue with distinctive properties and are quite different from TECs lining the TME microvasculature [ 93 , 104 ]. Therefore, 3D models including HUVECs do not strictly reflect organotypic tumour-vasculature crosstalk.…”

Section: Cell–cell Communicationsmentioning

confidence: 99%

See 2 more Smart Citations

Multicellular 3D Models to Study Tumour-Stroma Interactions

Colombo

Cattaneo

2021

IJMS

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Two-dimensional (2D) cell cultures have been the standard for many different applications, ranging from basic research to stem cell and cancer research to regenerative medicine, for most of the past century. Hence, almost all of our knowledge about fundamental biological processes has been provided by primary and established cell lines cultured in 2D monolayer. However, cells in tissues and organs do not exist as single entities, and life in multicellular organisms relies on the coordination of several cellular activities, which depend on cell–cell communication across different cell types and tissues. In addition, cells are embedded within a complex non-cellular structure known as the extracellular matrix (ECM), which anchors them in a three-dimensional (3D) formation. Likewise, tumour cells interact with their surrounding matrix and tissue, and the physical and biochemical properties of this microenvironment regulate cancer differentiation, proliferation, invasion, and metastasis. 2D models are unable to mimic the complex and dynamic interactions of the tumour microenvironment (TME) and ignore spatial cell–ECM and cell–cell interactions. Thus, multicellular 3D models are excellent tools to recapitulate in vitro the spatial dimension, cellular heterogeneity, and molecular networks of the TME. This review summarizes the biological significance of the cell–ECM and cell–cell interactions in the onset and progression of tumours and focuses on the requirement for these interactions to build up representative in vitro models for the study of the pathophysiology of cancer and for the design of more clinically relevant treatments.

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Section: Cell–cell Communicationsmentioning

confidence: 99%

Section: Cell–cell Communicationsmentioning

confidence: 99%

Section: Cell–cell Communicationsmentioning

confidence: 99%

See 1 more Smart Citation

Multicellular 3D Models to Study Tumour-Stroma Interactions

Colombo

Cattaneo

2021

IJMS

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“…As a consequence, leukocyte trafficking within the tumour microenvironment may well be more difficult than in healthy tissues. Moreover, endothelial cells in tumour sites can express the endothelin B receptor and its ligand endothelin-1 to trap T cell infiltrates [ 88 ]. Angiogenic factors in the tumour microenvironment such as TGF-β, VEGF, FGF, and nitric oxide could also inhibit the upregulation of cell adhesion molecules like ICAM-1, ICAM-2, VCAM-1, and CD34 on endothelial cells, rendering them refractory to immune cell infiltration [ 89 ].…”

Section: T Cell Recruitment and Regulationmentioning

confidence: 99%

Investigating T Cell Immunity in Cancer: Achievements and Prospects

Zeng

Chew

Cruz

et al. 2021

IJMS

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T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8+ Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models.

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“…(5,6,7) The tumors were interacting with other cells inside the nische including tumor associated broblast, tumor associated immunity or Tumor Associated Macrophages (TAM), tumor associated netrophils, endothelial cells and T cells which together contributed to tumor progressions. (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) This complex mechanism also in uenced tumor sensitivity towards distinct treatments such as radiotheraphy and chemotherapheutical agents. (18,19) Tumor microenvironment can be studied using biopsies samples to understanding celullar compositions as well as protein expression inside cell nische.…”

Section: Introductionmentioning

confidence: 99%

Predicting Gene Interactions in Tumor Microenvironment using Patient Derived Spheroid Primary Cell Culture

Abdullah

Utari

Nursyirwan

et al. 2021

Preprint

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Objective Cancer is a heterogenic disease from genetic to individual levels, which induced a variety of therapheutical research and disease progression. Cancer heterogeneity were also observed in most of solid tumors including colorectal cancer. Tumor growth depends on intra-tumoral complexity in which tumor cells surrounded by several cells in their nische known as tumor microenvironment. In this study, we are using spheroid derived primary culture derived from patients to predict expression pattern of tumor growth in their microenvironment in vitro. The gene list were data which obtained from our other “on going publications” Results In this study, we cultured patient-derived primary cells for 7 days and analyzed 24 genes that positively expressed in this in vitro system. Using STRING, we presented interactions between proteins which later may predict the interaction between the cells. The result shown that the cells actively using carbon metabolism to maintain energy, to produce several protection mechanism against oxidative stress to evade apoptosis, and to stimulate several protein related to epithelial to mesenchymal transition and angiogenesis in vitro.

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Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment – New Findings and Future Perspectives

Cited by 126 publications

References 186 publications

Multicellular 3D Models to Study Tumour-Stroma Interactions

Multicellular 3D Models to Study Tumour-Stroma Interactions

Investigating T Cell Immunity in Cancer: Achievements and Prospects

Predicting Gene Interactions in Tumor Microenvironment using Patient Derived Spheroid Primary Cell Culture

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