Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures
Menée à partir d'échantillons sanguins et de l'analyse transcriptomique spatiale d'échantillons tumoraux et d'échantillons tissulaires adjacents prélevés sur des patients atteints d'un carcinome hépatocellulaire, cette étude démontre que le métabolisme du tryptophane limite la maturation des structures lymphoïdes tertiaires intratumorales
Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates found in numerous cancers, often linked to enhanced immunotherapy responses and better clinical outcomes. However, the factors driving TLS maturation are not fully understood. Using near single-cell spatial transcriptomic mapping, we comprehensively profile TLSs under various maturation stages and their microenvironment in hepatocellular carcinoma (HCC). Based on their developmental trajectories, we classify immature TLSs into two groups: conforming and deviating TLSs. Our findings indicate that conforming TLSs, similar to mature TLSs, possess a niche function for immunotherapy responses, while deviating TLSs do not. We discover that the tryptophan-enriched metabolic microenvironment shaped by malignant cells contributes to the deviation of TLS maturation. Inhibiting tryptophan metabolism promotes intratumoral TLS maturation and enhances tumor control, synergizing with anti-PD-1 treatments. Therefore, promoting TLS maturation represents a potential strategy to improve antitumor responses and immunotherapy outcomes.
Cancer Cell , article en libre accès 2024