Paper Review

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates found in the tumor microenvironment (TME) and play a pivotal role in modulating antitumor immunity. They are often linked to enhanced immunotherapy responses and better clinical outcomes. However, understanding how these structures mature and how to boost their effectiveness has been challenging.

A recent study published in Cancer Cell, titled "Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures" used Stereo-seq spatial transcriptomics technology, to map and analyze TLSs in HCC at near-single-cell resolution. Scientists have, for the first time, mapped the panoramic development of tertiary lymphoid structures (TLSs) in hepatocellular carcinoma (HCC), the most common type of primary liver cancer. The study not only provides a detailed characterization of the unique features of TLSs in orchestrating antitumor immunity and modulating responses to immunotherapy but also reveals the critical regulatory role of tryptophan metabolism in TLS maturation. Stereo-seq helped see where these TLSs are, what cells are in them, and how they develop. The researchers analyzed 38 tissue sections, identifying 838 TLSs, and developed a novel classification scheme that categorizes immature TLSs into "conforming" and "deviating" types based on their developmental trajectories. It found that tumor-derived tryptophan metabolism restricts TLS maturation, particularly in "deviating" TLSs, which don't mature properly and reduce immune effectiveness. Inhibiting this metabolism showed promise in promoting TLS maturation and enhancing anti-PD-1 therapy, suggesting a new way to improve cancer treatment.

"To gain deeper insights into the roles of TLSs, several spatial profiling approaches, such as CODEX, Visium, and NanoString GeoMx DSP have been employed recently to characterize TLSs in situ. However, these methods have limitations, including restricted profiling breadth, suboptimal spatial resolution, and insufficient fields of view, which hinder the comprehensive characterization of TLSs and their microenvironment from extensive perspectives, " mentioned in the paper.
Discover more about the research: https://doi.org/10.1016/j.ccell.2025.03.011

About STOmics Stereo-seq:
STOmics now presents the upgraded Stereo-seq Transcriptomics Solution v1.3 launched in October 2024, featuring refined reagent chemistry, enhanced probe design, and optimized enzyme selection for whole transcriptome capturing of fresh frozen samples. This updated version delivers enhanced capture efficiency, broader compatibility, and a more streamlined workflow while minimizing the diffusion of mRNA molecules to achieve accurate spatial single-cell-level analysis.
Curious about STOmics Stereo-seq? https://en.stomics.tech/