Considering that PD-L2 and PD-L1 had different features in terms of expression timing and responses to chemotherapeutic drugs, evaluation of both PD-L2 and PD-L1 expression may be clinically important.BACKGROUND The small GTPase Ran is upregulated in multiple cancers and fundamental for cancer cell survival and progression, but its significance and molecular mechanisms in colorectal cancer (CRC) remain elusive. METHODS Ran expression was detected in CRC cell lines and tumour tissues. In vitro and in vivo functional assays were performed to examine the effects of Ran on cell proliferation and metastasis. The pathways and effectors regulated by Ran were explored by an unbiased screening. Bioinformatics prediction and experimental validation were used to identify the miRNA regulator for Ran. RESULTS Ran expression was frequently increased in metastatic CRC cells and tissues, especially in metastatic tissues. The upregulation of Ran correlated with poor CRC patient prognosis. Ran silencing reduced proliferation and metastasis of CRC cells both in vitro and in vivo. Ran regulated the expression of EGFR and activation of ERK and AKT signalling pathways. miR-802 was identified as an upstream regulator of Ran and miR-802 overexpression resulted in antiproliferative and antimetastatic activities. CONCLUSION Our study demonstrates the oncogenic roles and underlying mechanisms of Ran in CRC and the novel miR-802/Ran/EGFR regulatory axis may provide potential biomarkers for the treatment of CRC.BACKGROUND In 2018, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) issued revised recommendations for cancer prevention. We examined the relation between adherence to these recommendations and risk of total cancer in two population-based Swedish prospective cohorts (29,451 men and 25,349 women). METHODS Standardized-WCRF/AICR 2018 and simplified-WCRF/AICR 2018 adherence scores were constructed based on the WCRF/AICR recommendations for body weight, physical activity, diet, alcohol consumption and dietary supplement use. Data were collected using a self-administered questionnaire. RESULTS During the 15.4 years of follow-up, 12,693 incident cancers were ascertained. The multivariable HR between extreme categories of the Standardized-WCRF/AICR 2018 score (4.1-7 vs. 0-2) was 0.88 (95% CI = 0.82-0.95) and for the Simplified score (5-8 vs. 0-2) was 0.85 (95% CI = 0.80-0.90); each 1-score increment in recommendation adherence was associated with 3% (95% CI = 1-5%) and 4% (95% CI = 2-5%) decreased risk, respectively. Based on the Simplified scoring, most participants (>90%) did not meet WCRF/AICR 2018 recommendations regarding consumption of plant foods, limited consumption of red/processed meat and 'fast food'/processed food, and less then 50% of participants met the weight and physical activity recommendations. CONCLUSIONS Adherence to the 2018WCRF/AICR recommendations substantially reduced the risk of total cancer. Given that many people do not meet the recommendations, there is a great potential for cancer prevention.BACKGROUND Carbonic anhydrase IX (CA IX) is a hypoxia-induced enzyme regulating tumour pH and facilitating cell migration/invasion. It is primarily expressed as a transmembrane cell-surface protein, but its ectodomain can be shed by ADAM17 to extracellular space. This study aims to elucidate the impact of CA IX shedding on cancer cells. METHODS We generated a non-shed CA IX mutant by deletion of amino acids 393-402 from the stalk region and studied its phenotypic effects compared to full-length, shedding-competent CA IX using a range of assays based on immunodetection, confocal microscopy, in vitro real-time cell monitoring and in vivo tumour cell inoculation using xenografted NMRI and C57BL/6J female mice. RESULTS We demonstrated that the impairment of shedding does not alter the ability of CA IX to bind ADAM17, internalise, form oligomers and regulate pH, but induces cancer-promoting changes in extracellular proteome. Moreover, it affects intrinsic properties of cells expressing the non-shed variant, in terms of their increased ability to migrate, generate primary tumours and form metastatic lesions in lungs. CONCLUSIONS Our results show that the ectodomain shedding controls pro-tumorigenic and pro-metastatic roles of the cell-associated CA IX and suggest that this phenomenon should be considered when developing CA IX-targeted therapeutic strategies.BACKGROUND The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT572 CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC). METHODS A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS. RESULTS Two hundred and twenty-one patients were randomised and 190 (101 and 89 patients in the placebo and the Vx-001 arm, respectively) were analysed for efficacy. There was not treatment-related toxicity >grade 2. The study did not meet its primary endpoint (median OS 11.3 and 14.3 months for the placebo and the Vx-001, respectively; p = 0.86) whereas the median Time to Treatment Failure (TTF) was 3.5 and 3.6 months, respectively. Disease control for >6months was observed in 30 (33.7%) and 26 (25.7%) patients treated with Vx-001 and placebo, respectively. There was no documented objective CR or PR. https://www.selleckchem.com/products/bi-2493.html Long lasting TERT-specific immune response was observed in 29.2% of vaccinated patients who experienced a significantly longer OS compared to non-responders (21.3 and 13.4 months, respectively; p = 0.004). CONCLUSION Vx-001 could induce specific CD8+ immune response but failed to meet its primary endpoint. Subsequent studies have to be focused on the identification and treatment of subgroups of patients able to mount an effective immunological response to Vx-001. CLINICAL TRIAL REGISTRATION NCT01935154.