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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Related Experiment Video

Updated: May 29, 2025

Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments

Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments

Published on: April 30, 2021

Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing.

Alice Perucca¹, Andrea Gómez Llonín^2,3, Oriol Mañé Benach¹

¹Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.

Nature Communications

|February 3, 2025

Summary

A new in vitro model, MIRO, reveals how tumor microenvironment structures impact immunotherapy effectiveness. It shows stromal barriers cause immune exclusion, but IL2 therapy can overcome this to restore anti-cancer responses.

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Monitoring the Cancer-Immunity Cycle and Exploring Tumor Microenvironment Dynamics

Monitoring the Cancer-Immunity Cycle and Exploring Tumor Microenvironment Dynamics

Published on: June 7, 2024

Area of Science:

Oncology
Immunology
Biotechnology

Background:

Immunotherapies show variable efficacy in cancer patients.
Understanding tumor microenvironment (TME) interactions is crucial for improving treatment outcomes.
In vitro models are needed to study TME complexity and immune cell interactions.

Purpose of the Study:

To develop a novel in vitro platform, MIRO, for modeling the tumor/stroma interface and immune cell interactions.
To investigate the role of stromal barriers in immune exclusion and resistance to antibody-dependent cellular cytotoxicity (ADCC).
To evaluate the potential of interleukin-2 (IL2)-driven immunomodulation in overcoming TME-mediated immunosuppression.

Main Methods:

Development of MIRO, a fully humanized in vitro platform.
Spatial modeling of the tumor-stroma interface.
Assessment of immune cell interactions with cancer cells and stromal components.
Evaluation of targeted therapy efficacy and IL2-driven immunomodulation.

Main Results:

Stromal barriers were found to mediate immune exclusion, protecting cancer cells from ADCC.
IL2 administration enhanced immune cell velocity and spreading.
IL2-driven immunomodulation restored anti-cancer responses in models with refractory tumors.
MIRO platform demonstrated translational value in studying TME-driven therapy resistance.

Conclusions:

The MIRO platform provides a valuable tool for dissecting TME influences on immune responses.
Spatial organization of the TME significantly impacts immunotherapy sensitivity and resistance.
Targeted immunomodulation strategies, like IL2 therapy, can overcome stromal barriers to enhance anti-cancer immunity.