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First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m2) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48–0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53–0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov (NCT03958890).

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PurposeSystemic inflammation and immune dysfunction have been proved to be significantly associated with cancer progression and metastasis in colorectal cancer (CRC). The aim of this retrospective study was to investigate the association between preoperative systemic immune-inflammation index (SII) and postoperative liver metastasis in CRC.Patients and methodsThis retrospective study evaluated 182 patients with CRC who underwent surgical resection. The inflammation-based prognostic factors, including SII, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI), were calculated based on preoperative laboratory data. The univariate and multivariate logistic regression analysis was performed to identify the risk factors correlated with postoperative liver metastasis in CRC. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were respectively used to assess the predictive ability and clinical usefulness of SII for postoperative liver metastasis in CRC.ResultsThe univariate and multivariable analysis confirmed SII was independently correlated with postoperative liver metastasis in CRC (p<0.001), and the ROC and DCA analysis demonstrated SII was superior to other inflammation-based factors in terms of predictive ability.ConclusionSII is an independent predictive indicator of postoperative liver metastasis for patients with colorectal cancer.

PurposeTo characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.MethodsThe Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an in vivo assay, we used a model established with NPIdKO™ mice, which have a reconstituted immune system generated by transplanting PBMCs through intravenous injection, to evaluate the effect of metformin on tumors.ResultsThe TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway. In the coculture system, the metformin pretreatment group showed higher T cell activation and better T cell killing function than the control group. Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.ConclusionsMetformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.

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F(ab')(2) portion of the IgG is a functional fragment, which is responsible for the autoantibody interaction with platelet GPs in ITP, and some of them also affect platelet function, which can be used to develop completely humanized anti-GPIIb/IIIa small molecular phage antibody.

Oesophageal carcinoma (ESCA) is one of the most common digestive tract malignant tumours in the world. 1 Oesophageal squamous cell carcinomas (ESCC) is the main pathological type in China, especially in Henan province where there is a higher incidence. ESCC in its early stages often affects its functions only slightly, with no obvious symptoms. When they have clinical manifestations, most of the patients are in the advanced stage and have missed the chance of surgical treatment. Chemotherapy is an essential method to advanced