by Justin Jackson , Medical Xpress
Graphical abstract. Credit: Cell (2024). DOI: 10.1016/j.cell.2024.10.042
Institute of Immunobiology-led research has made a significant breakthrough in understanding how the body combats lung cancer. Their study reveals that specific cells, known as fibroblastic reticular cells (FRCs), create environments within tumors that help protect and activate immune cells to fight the cancer effectively.
Lung cancer remains one of the most challenging cancers to treat, in part because how it interacts with the immune system can be unpredictable. Some tumors attract a lot of T cell activity, while others do not. Understanding the factors influencing this interaction is crucial for developing better therapeutic strategies.
In the study, “Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer,” published in Cell, researchers analyzed human non-small cell lung cancer tissues using single-cell transcriptomics and high-resolution microscopy.
The team observed how FRCs develop through cell fate-mapping analyses and tested what happens when they remove them from tumors in mice. This helped assess the role of FRCs in the immune system’s cancer response.
They discovered that FRCs produce a chemical signal called CCL19, which attracts and organizes T cells within the tumor. FRCs were found to form interconnected networks within the tumor, creating dedicated microenvironmental niches where T cells gather to effectively attack cancer cells.
When the researchers removed these FRCs in mice, the immune response weakened, and the tumors grew more rapidly.
The study also found that these FRCs in tumors behave similarly to those found in healthy lymph nodes, where immune responses are typically organized and effective. This similarity suggests that tumors may retain some of the normal immune system related structures that are able to create favorable conditions for immune cells to fight cancer.
By targeting these protective FRCs to enhance their function, scientists hope to improve the effectiveness of existing immunotherapies. Future studies will explore how to manipulate these cells to boost immune responses in lung cancer patients, potentially leading to more effective and personalized treatments.
More information: Lucas Onder et al, Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer, Cell (2024). DOI: 10.1016/j.cell.2024.10.042
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