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Fibroblastic Reticular Cells – Their Influence on T Cell Environments & Lung Cancer Immunity

6 February 2025 6 min read byZEISS Microscopy

Introduction

Fibroblastic Reticular Cells in Lung Cancer and Their Role in Shaping Tumor Environments

Imagine looking through a microscope, entering in a hidden world where tiny T cells play a crucial role in the fight against lung cancer. At the Institute of Immunobiology at the Cantonal Hospital of St.Gallen (part of HOCH Health Ostschweiz), Switzerland, researchers are revealing how fibroblastic reticular cells (FRCs) shape the environment around tumors and influence T cells.

This exciting research not only changes the understanding of how the immune system works but may also open new possibilities for innovative therapies. One of the key researchers involved in this project is Dr. Lucas Onder. He is exploring the fascinating dynamics of FRCs and their potential to revolutionize cancer immunotherapy.

Two scientists in lab coats work in a lab; one looks into a microscope, the other works at a computer with screens displaying colorful images.

Evolution of Knowledge on Fibroblastic Reticular Cells in Immune Defense and Tumor Immunology

The research group of the Institute of Immunobiology focuses on immune defense against infectious agents, tumor immunology, and developmental immunology. Particularly, Lucas Onder and his colleagues investigate the interaction of fibroblastic reticular cells (FRCs) and immune cells during lymphoid organ development and in various diseases, such as cancer.
In doing so, they characterize FRCs. Their findings show that these cells are not only structural components of tissues: they are also active participants in immune responses, especially in the context of non-small cell lung cancer (NSCLC).

Until 20 years ago, the immunological role of fibroblasts was unclear. Early studies indicated that viral infections in mice affected the fibroblastic component of lymphoid organs, thereby impacting the effectiveness of the immune response and suggesting an immunological function of FRCs.
This discovery led to the creation of mouse models targeting FRCs and the creation of genetic tools for FRC-specific manipulation and imaging. Research has increased understanding of FRCs in mice and is now exploring their roles in human lymphoid organs and inflammatory tissues, like lung tumors. Future studies should identify FRC functions and factors for potential use in immunotherapy.

Microscopic image showing yellow and white structures on a black background, resembling nerve cells or neurons interconnected in a network-like pattern. — Tumor FRCs (orange) interacting with T cells (white).

Methodology, Technology, and Why FRCs Work Like a Good Orchestra Conductor

Utilizing advanced methodologies such as cell culture, immunological assays, and high-resolution imaging techniques, the research team investigates the interactions between FRCs and T cells. These methodologies allow for a deeper understanding of the cellular dynamics within the tumor microenvironment.

FRCs are sessile tissue cells that interact with immune cells, much like an orchestra conductor guiding musicians. They exist in distinct subpopulations, each exerting activating or attenuating effects on immune cells depending on the immunological context.

FRCs establish specialized microenvironments, creating niches for immune cells in lymphoid tissues and tumors. High-resolution imaging has revealed that FRCs closely interact with immune cells in the tumor microenvironment, driving immune defense in lung cancer by providing essential support to anti-tumor T lymphocytes, similar to how a conductor leads an orchestra to achieve a powerful performance.

Our extensive high resolution imaging approaches revealed that FRCs closely interact with immune cells in the tumor microenvironment, […] driving the immune defense in lung cancer by providing these distinct tissue niches to anti-tumor T lymphocytes - the cells that fight cancer cells.”

Dr. Lucas Onder Scientist/Expert in microscopy and flow cytometry, Medical Research Center, Cantonal Hospital of St.Gallen, Switzerland

Application Images

Confocal microscopy image showing a network of fibroblastic reticular cells in lymph nodes. Three-dimensional networks of FRCs in lymphoid organs provide a scaffold for immune cell migration & form distinct niches for immune cell activation.
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Confocal microscopy image depicting a histological section of a mouse lymph node. Three-dimensional networks of FRCs (green/red) pervade the whole lymph node & provide a scaffold for immune cell migration & form distinct niches for immune cell activation.
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Confocal microscopy image showing a lymph node anlage in a mouse embryo. FRC progenitors (green) develop around larger blood vessels (red) & the anlage is embedded in a web of capillaries (blue).
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Translating Research into Therapeutic Strategies

With their research and publication in Cell, the authors – Lucas Onder as first author – have made significant strides in understanding the tumor microenvironment. The importance of comprehending FRCs goes beyond basic research.

Understanding them in their entirety holds great promise for the development of therapeutic strategies aimed at increasing immunity against tumors. By creating a favorable environment for T cells, FRC-targeted therapies could revolutionize cancer immunotherapy.

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Our findings on FRCs in tumors may open avenues for the development of strategies that promote the anti-tumor immune environment to enhance anti-tumor immune responses. This may help to improve immunotherapies and make more cancers amenable to immunotherapy.

Dr. Lucas Onder

Two scientists in lab coats examine cellular images on computer screens in a research lab

A Vision for the Future

Lucas Onder and his colleagues demonstrate that FRCs are important for maintaining the immune system’s balance (homeostasis). Their findings highlight the potential of FRCs as promising target for cancer therapies. As our understanding in immunology evolves, insights from FRC research will be vital for developing effective cancer treatment strategies.

Ongoing research on FRCs relies on the collaboration among various research groups worldwide. FRCs are present in nearly all tissues where immune cells are active, indicating that studying FRCs can instruct many areas of immunological research. The scientific community is just beginning to understand FRC biology in human tissues, both in health and disease. Addressing this challenge requires teamwork among researchers.

New genetic models, innovative imaging techniques, and high-dimensional multi-omics will shape the future of FRC research. Additionally, the field should focus on expanding knowledge about human FRCs, particularly in diseased tissues. By combining genetic studies in model systems with observations in human tissues, researchers can significantly advance their understanding of FRCs.

We are only beginning to understand the nature of the different subpopulations of FRCs, with each population having different functions for the immune system. It will be exciting to study these subpopulations in more detail and I am sure we will find many surprises.

Dr. Lucas Onder

A landscaped urban garden with pathways, surrounded by modern buildings. People are walking and interacting. A helicopter is visible in the sky. — Cantonal Hospital of St.Gallen where the Medical Research Center is located.

How the Medical Research Center at St.Gallen is Shaping the Future of Medicine

The Medical Research Center (MFZ) at the Cantonal Hospital of St.Gallen integrates the Clinical Trials Unit (CTU), the Institute of Immunobiology, and clinical research laboratories.
This collaboration creates interfaces between clinical research and basic research, supporting a variety of research projects, including clinical trials and immunological studies.

Research initiatives: The Institute of Immunobiology leads innovative research initiatives while maintaining the MFZ's technical infrastructure, including advanced imaging technologies and laboratory facilities
Comprehensive services: The Clinical Trials Unit offers extensive services to assist clinical researchers in effectively implementing their projects

The Cantonal Hospital of St.Gallen is part of HOCH Health Ostschweiz, a company consisting of five hospitals in Eastern Switzerland.

LinkedIn profile of Dr. Lucas Onder
LinkedIn profile of HOCH Health Ostschweiz

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All images © HOCH Health Ostschweiz

Advanced imaging techniques, such as confocal microscopy, can be utilized to visualize the intricate networks of FRCs and their interactions with T cells in lymphoid tissues and the tumor microenvironment. These techniques allow for high-resolution imaging of FRCs and their roles in immune cell activation.
Researchers employ various methodologies, including cell culture, immunological assays, and high-resolution imaging techniques, to investigate the interactions between FRCs and immune cells. These approaches help elucidate the cellular dynamics within the tumor microenvironment.
Insights from FRC studies can lead to the identification of new therapeutic strategies that enhance the immune response against tumors. By understanding how FRCs create supportive environments for T cells, researchers can develop targeted therapies that improve the efficacy of cancer immunotherapy.