Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer
Onder et al., Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer, Cell (2025).
Credits for Summary: Khyati Shukla Aakash Khurana
This research investigates the role of fibroblastic reticular cells (FRCs) in the tumor microenvironment of non-small cell lung cancer (NSCLC), focusing on how these cells contribute to T cell environments that can either support or inhibit anti-tumor immunity. The study involved patients undergoing surgical resection of lung lobes, with samples processed for cell isolation and analysis using techniques such as flow cytometry and single-cell RNA sequencing (scRNA-seq). The findings reveal that FRCs, particularly CCL19-expressing subsets, originate from healthy lung tissue and differentiate into tumor-associated reticular cells (TRCs) and proliferative reticular cells (PRCs).
The results indicate that TRCs and PRCs play critical roles in modulating the activity of CD8+ T cells, with interactions between these immune cells and FRCs influencing T cell differentiation and function. The study found that specific gene sets were enriched in exhausted and cycling CD8+ T cells, highlighting distinct functional states shaped by the tumor microenvironment. Furthermore, disrupting FRC-immune cell interactions led to decreased anti-tumor activity of CD8+ T cells and promoted tumor growth, underscoring the essential role of FRCs in maintaining protective immunity.
In conclusion, the research emphasizes the significance of FRCs in lung cancer and their dual role in supporting T cell activity while being influenced by tumor dynamics. Targeting FRCs or enhancing their interactions with T cells may offer potential therapeutic strategies to improve anti-tumor immunity. Overall, this study provides valuable insights into the complex immune cell interactions within tumors, paving the way for future research aimed at leveraging the immune system for effective cancer treatments.