BackgroundAs a novel immune checkpoint, CD73 has been reported to play prominent roles in several malignancies. However, the significance of CD73 in melanoma remains ambiguous. This study sought to reveal the impact of CD73 on the tumor microenvironment (TME) and patients’ prognosis, and to investigate whether CD73 could be a therapeutic target in Chinese melanomas, which were dominated by acral and mucosal subtypes.MethodsTwo independent Chinese cohorts of 194 patients with melanoma were enrolled. CD73 and PD-L1 expression as well as CD8+ and CD56+ cell infiltrations were evaluated by immunohistochemistry in 194 resected melanoma samples. Clinical outcomes of patients were assessed utilizing the Kaplan-Meier plotter and Cox proportional hazard analysis. RNA-seq data was obtained from TCGA database. Gene set functional annotations were performed based on GO, KEGG and GSEA analysis. CIBERSORT, ssGSEA and TIMER were used to explore the association between CD73 and immune infiltration. These findings were validated by establishing tumor xenograft model, and functions of tumor-infiltrating immune cells were examined by flow cytometry and immunofluorescence.ResultsHigh CD73 expression showed poorer clinical outcomes and was identified as an independent prognostic indicator for survival in two cohorts. Expression of CD73 was more prevalent than PD-L1 in Chinese melanoma cohorts (54.6% vs 23.2%). Co-expression of both immune checkpoints was infrequent (12.9%) in melanoma, and 54.4% of PD-L1 negative cases showed elevated expression of CD73. CD73high tumors showed a microenvironment with fewer CD8+ T cells and CD56+ NK cells infiltration, which displayed a dysfunctional phenotype. With the treatment of CD73 inhibitor APCP, the amount of CD8+ T cells and CD56+ NK cells infiltrated in tumors was elevated and the immunosuppressive effect of CD73 was eliminated.ConclusionsHigh CD73 expression was associated with an inhibitory TME and adverse clinical outcomes of melanoma. In comparison to PD-L1, CD73 was more prevalent and possessed more definite prognostic significance. Therefore, it may serve as a prognostic indicator and immunotherapeutic target next to PD-L1 in melanoma for Chinese population.
BackgroundThe study aimed to build and validate practical nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with synovial sarcoma (SyS).MethodsA total of 893 eligible patients confirmed to have SyS between 2007 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n = 448) and validation cohort (n = 445). Clinically independent prognostic and important factors were determined according to the Akaike information criterion in multivariate Cox regression models when developing the nomograms with the training cohort. The predictive accuracy of nomograms was bootstrapped validated internally and externally with the concordance index (C-index) and calibration curve. Decision curve analysis (DCA) was performed to compare the clinical usefulness between nomograms and American Joint Commission on Cancer (AJCC) staging system.ResultsTwo nomograms shared common indicators including age, insurance status, tumor site, tumor size, SEER stage, surgery, and radiation, while marital status and tumor site were only included into the OS nomogram. The C-index of nomograms for predicting OS and CSS was 0.819 (0.873–0.764) and 0.821 (0.876–0.766), respectively, suggesting satisfactory predictive performance. Internal and external calibration curves exhibited optimal agreement between the nomogram prediction and the actual survival. Additionally, DCA demonstrated that our nomograms had obvious superiority over the AJCC staging system with more clinical net benefits.ConclusionsTwo nomograms predicting 3- and 5-year OS and CSS of SyS patients were successfully constructed and validated for the first time, with higher predictive accuracy and clinical values than the AJCC staging system regarding OS and CSS.
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