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BackgroundImmunotherapy has achieved great success in cancer. Nevertheless, many patients cannot benefit from immune checkpoint blockade therapy because of the scantiness of CD8+ T cell infiltration in the tumor microenvironment (TME). CXCL11 is known as a regulator that influences T-cell infiltration into tumors. However, the role of CXCL11 in pan-cancer is still unclear.MethodsIn this study, we investigated the expression and function of CXCL11 across 33 types of cancers based on datasets from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. We analyzed the CXCL11 differential expression in tumor tissue and nontumoral tissue and in different stages of cancers. Moreover, the correlations among CXCL11 expression, prognosis, mismatch repair, tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, and immune-related genes were evaluated.ResultsCXCL11 expression was significantly higher in tumoral tissue than in nontumoral tissue for most types of cancer. Improved CXCL11 expression was related to an inconsistent prognosis in different cancers. CXCL11 was positively associated with CD8+ T cells and T follicular helper cells in the TME. High expression of CXCL11 was positively related to TMB in BLCA, BRCA, CESC, COAD, LGG, LUAD, OV, SKCM, STAD, THYM, and UCEC. A positive correlation between CXCL11 and MSI was found in COAD and UVM. Moreover, functional analysis of CXCL11 showed that high CXCL11 expression was significantly related to immune-relevant pathways.ConclusionsCXCL11 might function as a prognostic and immunotherapy marker across cancers. Further investigation into CXCL11 might provide promising insights to improve cancer therapy.

BackgroundGallbladder cancer (GBC) is a mortal malignancy with limited therapeutic strategies. We aimed to develop novel immune scoring systems focusing on B7-H3, B7-H4, and HHLA2. We further investigated their potential clinical effects in predicting survival and immunotherapeutic efficacy for GBC.MethodsThis was a retrospective cohort study in a single center that explored the expression characteristics of B7-H3, B7-H4, and HHLA2. The immune scoring nomograms for prognostic were developed via logistic regression analyses. Their performance was evaluated using the Harrell concordance index (C-index) and decision curves analysis (DCA), and validated with calibration curves.ResultsB7-H3, B7-H4, and HHLA2 manifested with a relatively high rate of co-expression patterns in GBC tissues. They were associated with worse clinicopathological stage, suppression of immune microenvironment, and unfavorable prognosis in postoperative survival. B7 stratification established based on B7-H3, B7-H4, and HHLA2 was an independent prognostic predictor (p<0.05 in both groups). Moreover, immune stratification was also successfully constructed based on B7 stratification and the density of CD8+ TILs (all p<0.001). The prediction models were developed based on B7-/or immune stratification combined with the TNM/or Nevin staging system. These novel models have excellent discrimination ability in predicting survival and immunotherapeutic efficacy for GBC patients by DCA and clinical impact plots. Finally, dynamic nomograms were developed for the most promising clinical prediction models (B7-TNM model and Immune-TNM model) to facilitate prediction.ConclusionsImmune scoring systems focusing on B7-H3, B7-H4, and HHLA2 may effectively stratify the prognosis of GBC. Prognostic nomograms based on novel immune scoring systems may potentially predict survival and immunotherapeutic efficacy in GBC. Further valid verification is necessary.