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.

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.

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.”

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.

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.