Transcriptome analysis of tertiary lymphoid structures (TLSs)-related genes reveals prognostic value and immunotherapeutic potential in cancer

Abstract

Abstract Objectives Tertiary lymphoid structures (TLSs) are increasingly recognized as pivotal formations in antitumor immunity, with many mature TLSs relating to favorable prognosis in a variety of cancers. Analysis of the transcriptome data provided an opportunity to investigate the relationship between TLSs and the clinical outcomes of patients. Methods We performed transcriptome analysis to examine the expression patterns of 79 TLS-related genes within 32 cancers from The Cancer Genome Atlas, correlating these patterns to the clinical outcomes of patients. To improve the analysis, we developed a novel prognostic signature (TLSig) and validated its robust performance via multiple independent cancer cohorts. Results Our results demonstrated that the expression of TLS-related genes exhibited significant heterogeneity across cancers; and that TLSig was significantly associated with patient prognosis within most cancer types. Specifically, TLSig expressed potential prediction of whether patients would benefit from immunotherapy and presented significant interactions with epithelial to mesenchymal transition (EMT) and the cell cycle. Moreover, a difference in the distribution of TLSs between tumor and nontumor tissues was observed, which was validated in hepatocellular carcinoma (HCC) samples. We further investigated the potential mechanism for the difference in the distribution of TLSs between tumor and nontumor tissues of HCC, and observed the connection between TLSs and human leucocyte antigen (HLA). Conclusions In summary, our results demonstrated the prognostic value of TLSs in predicting patient prognosis and provided new insights into the molecular mechanism of TLSs in cancer.