Intratumor tertiary lymphoid structures (TLSs) are emergingly associated with immunotherapy efficacy and clinical outcomes. Mature TLSs within tumors are correlated with improved prognoses and enhanced responses to immunotherapy, whereas immature or absent TLSs are linked to poorer outcomes.
Here, we develop a novel strategy ciTLSs that enables comprehensively mapping TLSs in an in situ context and simultaneously deciphering their microenvironment using spatial transcriptomic profiles with a broad view of tissue at a cellular resolution generated by Stereo-seq. By implementing the strategy, we represent a comprehensive spatially resolved characterization of an unprecedented number of TLS from hepatocellular carcinoma (HCC) patients.
Moreover, We devised a novel classification schematic to categorize the canonical immature TLSs into conforming and deviating TLS groups based on their developmental trajectories in relation to the TLS maturation process. Intriguingly, we discovered that the metabolic microenvironment shaped by malignant cells contributes to the heterogeneity of TLS maturation, with increased tryptophan metabolism driving the TLS deviation.
In this repository, you could access to the code used to analysis the Stereo-seq, scRNA-seq and scATAC-seq data from the associated manuscript.
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Video and scripts for TLS identification using spatial transcriptomics are avaliable in 001.TLS_Identification
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Notebooks for how to classify different developmental stages of TLSs are avaliable in 002.TLS_Classification
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Notebooks for celltypes or subtypes annotation are available in 003.Celltype_Annotation
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Notebooks for all main figures are available in 004.Main_Figures
All genomics data reported in this study have been deposited at the Genome Sequence Archive at the National Genomics Data Center (Beijing, China) under the BioProject ID PRJCA017662.
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