An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

Al-Hity, Gheed; Yang, Feng; Campillo-Funollet, Eduard; Greenstein, Andrew E.; Hunt, Hazel; Mampay, Myrthe; Intabli, Haya; Falcinelli, Marta; Madzvamuse, Anotida; Venkataraman, Chandrasekhar; Flint, Melanie S.

doi:10.1038/s42003-021-02296-7

Cited by 18 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, tumour cells can produce anti-inflammatory cytokines that promote growth, attenuate apoptosis and facilitate metastasis. In the experiments reported in [7], cortisol downregulated IFN-γ and upregulated IL-10. IFN-γ is a pro-inflammatory cytokine that stimulates immune response, through T cell trafficking in the tumour-microenvironment and infiltration [9,10], whereas IL-10 is an anti-inflammatory cytokine that inhibits immune response by reducing T cell proliferation [11,12].…”

Section: Introductionmentioning

confidence: 89%

“…In [7], the authors developed a 3D in vitro model to explore the effects of the stress hormone cortisol on immune cell infiltration into tumour spheroids.…”

Section: Introductionmentioning

confidence: 99%

“…In light of these considerations, and motivated by in vitro experimental observations in co-culture between cancer spheroids and immune cells [7], in this paper we develop an IBM to study the effect of psychological stress on immune infiltration. The model builds on our previous work [27] and is calibrated to qualitatively reproduce, in silico, the experimental results presented in [7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An individual-based model to explore the impact of psychological stress on immune infiltration into tumour spheroids

Leschiera,

Al-Hity,

Flint

et al. 2024

Phys. Biol.

Self Cite

View full text Add to dashboard Cite

In recent in vitro experiments on co-culture between breast tumour spheroids and activated immune cells, it was observed that the introduction of the stress hormone cortisol resulted in a decreased immune cell infiltration into the spheroids. Moreover, the presence of cortisol deregulated the normal levels of the pro- and anti-inflammatory cytokines IFN-γ and IL-10. We present an individual-based model to explore the interaction dynamics between tumour and immune cells under psychological stress conditions. With our model, we explore the processes underlying the emergence of different levels of immune infiltration, with particular focus on the biological mechanisms regulated by IFN-γ and IL-10. The set-up of numerical simulations is defined to mimic the scenarios considered in the experimental study. Similarly to the experimental quantitative analysis, we compute a score that quantifies the level of immune cell infiltration into the tumour. The results of numerical simulations indicate that the motility of immune cells, their capability to infiltrate through tumour cells, their growth rate and the interplay between these cell parameters can affect the level of immune cell infiltration in different ways. Ultimately, numerical simulations of this model support a deeper understanding of the impact of biological stress-induced mechanisms on immune infiltration.

show abstract

Section: Introductionmentioning

confidence: 89%

“…In [7], the authors developed a 3D in vitro model to explore the effects of the stress hormone cortisol on immune cell infiltration into tumour spheroids.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An individual-based model to explore the impact of psychological stress on immune infiltration into tumour spheroids

Leschiera,

Al-Hity,

Flint

et al. 2024

Phys. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the low complexity of this system may not fully recapitulate the events in the TME. For example, Gheed Al-Hity et al developed a 3D coculture model by coculturing breast tumor spheroid and splenocytes isolated from mice that contain B cells, T cells, and DCs, which was used to study the effect of stress hormones on immune infiltration and tumor growth [Al-Hity et al, 2021]. However, this model did not incorporate important barriers in the TME that limits tumor infiltration such as stroma, vasculature, regulatory T cells, etc.…”

Section: De Novo Generation Of Tumor Organoidsmentioning

confidence: 99%

Give them vasculature and immune cells – how to fill the gap of organoids

Yip¹,

Wang²,

Sugimura³

2023

Cells Tissues Organs

View full text Add to dashboard Cite

Valid and relevant models are critical for research to have biological relevance or proceed in the right path. As well-established 2D cell cultures lack niches and cues and rodent models differ in species, 3D organoids emerged as a powerful platform for research. Cultured in vitro from stem cells, organoids are heterogeneous in cells and closely resemble the in vivo settings. Organoids also recapitulate the unique human features if cultured from a human source and are subject to genetic modification. However, one type of organoid possesses only a limited selection of cells. In particular, the absence of vasculature and immune cells restricts the organoids from nutrition, cues, or critical interactions, undermining the validity of organoids as physiological or pathological models. To fill the current gap, there is an urgent need to provide organoids with vasculature and immune cells. In this paper, we review the methods to generate physiological and pathological organoid models and summarize ways to vascularize or immunize them. Our discussion continues with some advantages and disadvantages of each method and some emerging solutions to current problems.

show abstract

“…3D in vitro models may provide a viable solution as they can help reduce animal experiments during preclinical studies, accelerate therapeutic target discovery, cut down R&D spending and potentially decrease spending on global cancer care ( 18 , 19 ). By creating functional tissue structures that accurately mimic human biology, 3D in vitro models allow researchers not only to study disease progression, but also test different therapeutics directly in vitro , which could drastically shorten drug development timelines ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions

et al. 2023

View full text Add to dashboard Cite

Augmenting adaptive immunity is a critical goal for developing next-generation cancer therapies. T and B cells infiltrating the tumor dramatically influence cancer progression through complex interactions with the local microenvironment. Cancer cells evade and limit these immune responses by hijacking normal immunologic pathways. Current experimental models using conventional primary cells, cell lines, or animals have limitations for studying cancer-immune interactions directly relevant to human biology and clinical translation. Therefore, engineering methods to emulate such interplay at local and systemic levels are crucial to expedite the development of better therapies and diagnostic tools. In this review, we discuss the challenges, recent advances, and future directions toward engineering the tumor-immune microenvironment (TME), including key elements of adaptive immunity. We first offer an overview of the recent research that has advanced our understanding of the role of the adaptive immune system in the tumor microenvironment. Next, we discuss recent developments in 3D in-vitro models and engineering approaches that have been used to study the interaction of cancer and stromal cells with B and T lymphocytes. We summarize recent advancement in 3D bioengineering and discuss the need for 3D tumor models that better incorporate elements of the complex interplay of adaptive immunity and the tumor microenvironment. Finally, we provide a perspective on current challenges and future directions for modeling cancer-immune interactions aimed at identifying new biological targets for diagnostics and therapeutics.

show abstract

An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

Cited by 18 publications

References 39 publications

An individual-based model to explore the impact of psychological stress on immune infiltration into tumour spheroids

An individual-based model to explore the impact of psychological stress on immune infiltration into tumour spheroids

Give them vasculature and immune cells – how to fill the gap of organoids

Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions

Contact Info

Product

Resources

About