Drugs blocking programmed death ligand‐1 (PD‐L1) have shown unprecedented activity in metastatic and unresectable bladder cancer. The purpose of the present study was to investigate the expression, clinical significance and association of PD‐L1 with tumor‐infiltrating lymphocytes (TIL) in resectable urothelial cell carcinoma of the bladder (UCB). In this retrospective study, 248 UCB patients who received radical cystectomy or transurethral resection were examined. Immunohistochemistry was used to evaluate PD‐L1 expression and stromal CD8+ TIL, Th1 orientation T cell (T‐bet+) and PD‐1+ TIL densities within the intratumoral regions and associated stromal regions. Of the 248 specimens, 23% showed PD‐L1 expression in tumor cells and 55% in tumor‐infiltrating immune cells. CD8+ TIL, T‐bet+ TIL and PD‐1+ TIL were distributed throughout the tumor tissues and were more frequently distributed in stromal regions than in intratumoral regions. PD‐L1+ tumor cells and PD‐L1+ immune cells were positively associated with aggressive clinical features (all P < .05). Both PD‐L1+ tumor cells and PD‐L1+ immune cells were associated with poorer recurrence‐free and overall survival (all P < .05). Multivariate analysis showed that PD‐L1+ immune cells were an independent prognostic factor for overall (P = .001) and recurrence‐free survival (P = .024). Notably, high stromal CD8+ TIL and PD‐1+ TIL density were associated with poorer overall survival (P = .031 and P = .001, respectively). In the stroma, CD8+ TIL density has strong positive association with PD‐L1+ immune cells and PD‐1+ TIL density (all P < .0001). These results suggested that an exhausted immune state occurred in the tumor stroma in UCB. Further clinical development of immune‐checkpoint inhibitors may be effective for resectable patients with UCB.

Ovarian carcinoma is a lethal gynecological malignancy. Women with ovarian cancer (OC) are highly recurrent and typically diagnosed at late stage. Ten-eleven translocation protein 3 (TET3) belongs to the family of ten-eleven translocations (TETs) which induce DNA demethylation and gene regulation in epigenetic level by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Previous studies indicated that TET3 is overexpressed in ovarian cancer tissues. However, the clinic-pathological functions and prognostic values of TET3 remain unclear. Here we performed an integrative study to identify the role of TET3 by bioinformatics analysis. The TET3 expression in ovarian cancer was assessed with Oncomine database, and validated with TCGA and GTEx database. The correlation of TET3 gene alteration and clinic-pathological functions was addressed by integrative analysis of GEO datasets. Then we showed mainly TET3 gain and diploid but less deletion in ovarian cancer by copy number alteration (CNA) or mutation analysis with cBioPortal. Furthermore, by using Kaplan-Meier plotter (K-M plotter), we evaluated that high TET3 level was associated with poor survival in ovarian cancer patients, which was validated with analysis by PrognoScan database and gene differential analyses with TCGA and GTEx. This is the first study demonstrated that elevated expression of TET3 is associated with poor clinic-pathological functions, poor prognosis, wherein TET3, which presents epigenetic changes or methylation changes, might be served as a diagnostic marker or therapeutic target for ovarian cancer.

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This retrospective study found a possible association between CG and IC, and coexisting OLUTDs influenced this association.