IntroductionCholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium with a poor prognosis. The lack of biomarkers to predict therapeutic response and prognosis is one of the major challenges for CCA treatment. Tertiary lymphoid structures (TLS) provide a local and pivotal microenvironment for tumor immune responses. The prognostic value and clinical relevance of TLS in CCA remain unclear. We aimed to explore the characteristics and clinical significance of TLS in CCA.MethodsWe investigated the prognostic value and clinical relevance of TLS in CCA using a surgery cohort containing 471 CCA patients (cohort 1) and an immunotherapy cohort containing 100 CCA patients (cohort 2). Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to evaluate the maturity of TLS. Multiplex IHC (mIHC) was employed to characterize the composition of TLS.ResultsDifferent maturity of TLS were observed in CCA tissue sections. Strong staining of the four-gene signature including PAX5, TCL1A, TNFRSF13C, and CD79A were found in TLS regions. A high density of intra-tumoral TLS (T-score high) were significantly correlated with longer overall survival (OS) both in CCA cohort 1 (p = 0.002) and cohort 2 (p = 0.01), whereas a high density of peri-tumoral TLS (P-score high) were associated with shorter OS in these two cohorts (p = 0.003 and p = 0.03, respectively).ConclusionThe established four-gene signature efficiently identified the TLS in CCA tissues. The abundance and spatial distribution of TLS were significantly correlated with the prognosis and immune checkpoint inhibitors (ICIs) immunotherapy response of CCA patients. The presence of intra-tumoral TLS are positive prognostic factors for CCA, which provide a theoretical basis for the future diagnosis and treatment of CCA.

Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums.

Neuroblastoma is the most common extracranial solid tumor in children. Tumor metastasis in high-risk NB patients is an essential problem that impairs the survival of patients. In this study, we aimed to use a comprehensive bioinformatics analysis to identify differentially expressed genes between NB and control cells, and to explore novel prognostic markers or treatment targets in tumors. In this way, FN1, PIK3R5, LPAR6 and LPAR1 were screened out via KEGG, GO and PPI network analysis, and we verified the expression and function of LPAR1 experimentally. Our research verified the decreased expression of LPAR1 in NB cells, and the tumor migration inhibitory effects of LPA on NB cells via LPAR1. Moreover, knockdown of LPAR1 promoted NB cell migration and abolished the migration-inhibitory effects mediated by LPA-LPAR1. The tumor-suppressing effects of the LPA-LPAR1 axis suggest that LPAR1 might be a potential target for future treatment of NB.