We are pleased to share that Stromal Therapeutics have published groundbreaking research in Cell, shedding light on a critical interplay between fibroblasts and the local immune environment.
The study reveals the pivotal role of CCL19-expressing fibroblastic reticular cells in shaping T cell activity within the tumor microenvironment.
Stromal Therapeutics focuses on developing new generation immunotherapies against tissue cytokines and their inhibitors, produced by stromal cells. Tissue cytokines are regulated at sites of inflammation, identifying this family of molecules as locally acting, drugable targets in chronic diseases. Stromal Therapeutics’ lead compound demonstrates efficacy in preclinical models of inflammatory heart disease, an indication that has no specific therapy in patients.
As the newly published study highlights the importance of the interplay between the stromal tissue fibroblasts with T cells environment and functionality in tumors, we are looking forward to future possible pipeline extension to oncology.
Congratulations to the whole team on this achievement.
Abstract:
Stringent control of T cell activity in the tumor microenvironment is essential for the generation of protective antitumor immunity. However, the identity, differentiation, and functions of the cells that create critical fibroblastic niches promoting tumor-infiltrating T cells remain elusive. Here, we show that CCL19-expressing fibroblastic reticular cells (FRCs) generate interconnected T cell environments (TEs) in human non-small cell lung cancer, including tertiary lymphoid structures and T cell tracks. Analysis of the FRC-T cell interactome in TEs indicated molecular networks regulating niche-specific differentiation of CCL19-expressing fibroblasts and T cell activation pathways. Single-cell transcriptomics and cell fate-mapping analyses in mice confirmed that FRCs in TEs originate from mural and adventitial progenitors. Ablation of intratumoral FRC precursors decreased antitumor T cell activity, resulting in reduced tumor control during coronavirus vector-based immunotherapy. In summary, specialized FRC niches in the tumor microenvironment govern the quality and extent of antitumor T cell immunity.
Continue reading the paper here.
