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Objectives: Subepithelial lesions (SELs) are associated with various endoscopic resection (ER) outcomes and diagnostic challenges. We aimed to establish a tool for predicting ER‐related outcomes and diagnosing SELs and to investigate the predictive value of endoscopic ultrasound (EUS). Methods: Phase 1 (system development) was performed in a retrospective cohort (n = 837) who underwent EUS before ER for SELs at eight hospitals. Prediction models for five key outcomes were developed using logistic regression. Models with satisfactory internal validation performance were included in a mobile application system, SEL endoscopic resection predictor (SELERP). In Phase 2, the models were externally validated in a prospective cohort of 200 patients. Results: An SELERP was developed using EUS characteristics, which included 10 models for five key outcomes: post‐ER ulcer management, short procedure time, long hospital stay, high medication costs, and diagnosis of SELs. In Phase 1, 10 models were derived and validated (C‐statistics, 0.67–0.99; calibration‐in‐the‐large, −0.14–0.10; calibration slopes, 0.92–1.08). In Phase 2, the derived risk prediction models showed convincing discrimination (C‐statistics, 0.64–0.73) and calibration (calibration‐in‐the‐large, −0.02–0.05; calibration slopes, 1.01–1.09) in the prospective cohort. The sensitivities and specificities of the five diagnostic models were 68.3–95.7% and 64.1–83.3%, respectively. Conclusion: We developed and prospectively validated an application system for the prediction of ER outcomes and diagnosis of SELs, which could aid clinical decision‐making and facilitate patient–physician consultation. EUS features significantly contributed to the prediction. Trial registration: Chinese Clinical Trial Registry, http://www.chictr.org.cn (ChiCTR2000040118). [ABSTRACT FROM AUTHOR]

The follicular CXCR5 + CD8 + T cells have recently emerged as a critical cell type in mediating peripheral tolerance as well as antiviral immune responses during chronic infections. In this study, we investigated the function of CXCR5 + CD8 + T cells in HBV-related hepatocellular carcinoma patients. Compared to CXCR5 − CD8 + T cells, CXCR5 + CD8 + T cells presented elevated PD-1 expression but reduced Tim-3 and CTLA-4 expression. Upon anti-CD3/CD28 stimulation, CXCR5 + CD8 + T cells demonstrated higher proliferation potency than CXCR5 − CD8 + T cells, especially after PD-1 blockade. CXCR5 + CD8 + T cells also demonstrated significantly higher granzyme B synthesis and release, as well as higher level of degranulation. Tumor cells were more readily eliminated by CXCR5 + CD8 + T cells than by CXCR5 − CD8 + T cells. Interestingly, we found that B cells were more resistant to CXCR5 + CD8 + T cell-mediated killing than tumor cells, possibly through IL-10-mediated protection. In addition, the CXCR5 + CD8 + T cell-mediated cytotoxic effects on tumor cells could be significantly enhanced by PD-L1 blockade. Together, we presented that in patients with in HBV-related hepatocellular carcinoma, CXCR5 + CD8 + T cells could mediate tumor cell death more potently than the CXCR5 − CD8 + T cells in vitro while the autologous B cells were protected. [ABSTRACT FROM AUTHOR]

The tumor-associated immune response is governed by the signalling events of various regulatory molecules, one of which is the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). In conventional T cells, CTLA-4 could outcompete CD28 in binding to CD80/86 but does not produce a co-stimulatory signal, resulting in T cell anergy. CTLA-4 in regulatory T cells (Tregs) could also function in a cell-extrinsic fashion by removing CD80/CD86 from the antigen-presenting cells (APCs), thus preventing further priming of other T cells. In this study, we examined the role of CTLA-4 in CD4 + T cell subsets from pancreatic cancer patients. In circulating CD4 + T cells, the expression of CTLA-4 was low at baseline but was significantly upregulated following T cell stimulation. Interestingly, the CTLA-4-expressing CD4 + T cells at baseline were overwhelmingly FOXP3-expressing. With the increase of T cell stimulation, the proportion of ROR gamma t-expressing CD4 + T cells was progressively increased. By CD25 vs. CCR6 staining, the CD25 + CCR6 + and the CD25 + CCR6 - CD4 + T cells both presented high levels of CTLA-4 expression, but only the CD25 + CCR6 + and the CD25 - CCR6 + expressed significant amounts of IL-17. When incubated with autologous CD8 + T cells, the CD25 + CCR6 + Th17 cells presented significantly higher suppressive function than the CD25 - CCR6 + Th17 cells in a CTLA-4-dependent manner. Finally, the CTLA-4-expressing Th17 cells were present at higher levels in the tumor-infiltrating lymphocytes than in circulating blood. Overall, these data suggest that CTLA-4 expressing Th17 cells may present regulatory activities in pancreatic cancer patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)