miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42.

TIGIT, an immune checkpoint molecule widely expressed on NK cells, activated T cells and Tregs, has been involved in delivering inhibitory signals through the interaction with PVR. The blockade of TIGIT/PVR interaction is a promising approach in cancer immunotherapy. Here, we unexpectedly discovered the expression of TIGIT in murine tumor cells. To elucidate the mechanism of such intrinsic expression, TIGIT knockout murine colorectal CT26 and MC38 cell lines were generated by using CRISPR/Cas9 system. Although TIGIT knockout showed no effects on proliferation and colony formation of tumor cells in vitro, the tumor growth in mice was considerably inhibited. TIGIT knockout led to the increase of IFN-γ secretion by NK and CD8+ T cells. Further, in BABL/c nude mice, CD8+ T cells depleting mice and NK cells depleting nude mice, the promotion of tumor growth was significantly diminished, suggesting that both NK cells and CD8+ T cells were involved in the tumor promoting process mediated by intrinsic TIGIT. In addition, blocking TIGIT/PVR interaction by the antibody or recombinant PVR protein could elicit anti-tumor effects by facilitating the tumor infiltration and restoring the function of CD8+ T cells, and the antibody-mediate TIGIT blockade could inhibit MC38 tumor growth through blocking TIGIT expressed on tumor cells. We therefore propose a novel TIGIT/PVR interaction mode that tumor intrinsic TIGIT delivers inhibitory signals to CD8+ T cells and NK cells by engaging with PVR.

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The mortality benefit of esophageal squamous cell carcinoma (ESCC) screening has been reported in several studies; however, the results of ESCC screening programs in China are suboptimal. Our study aimed to develop an ESCC risk prediction model to identify high-risk individuals for population-based esophageal cancer screening. In total, 86 745 participants enrolled in a population-based esophageal cancer screening program in rural China between 2007 and 2012 were included in the present study and followed up until December 31, 2015. Models for identifying individuals at risk of ESCC within 3 years were created using logistic regressions. The area under the receiver operating curve (AUC) was determined to estimate the model's overall performance. A total of 298 individuals were diagnosed with ESCC within 3 years after baseline. The model of ESCC included the predictors of age, sex, family history of upper gastrointestinal cancer, smoking status, alarming symptoms of retrosternal pain, back pain or neck pain, consumption of salted food and fresh fruits and disease Abbreviations: +LR, positive likelihood ratio; AUC, area under the receiver operating curve; BMI, body mass index; CI, confidence interval; ESCC, esophageal squamous cell carcinoma; −LR, negative likelihood ratio; NNS, number needed to screen; NPV, negative predictive value; OR, odds ratio; PPV, positive predictive value; UGI, upper gastrointestinal. Wanqing Chen and He Li contributed equally to this study.