Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

Novel biomarkers for patient stratification in colorectal cancer:A review of definitions,emerging concepts,and data

Colorectal cancer(CRC) treatment has become more personalised,incorporating a combination of the individual patient risk assessment,gene testing,and chemotherapy with surgery for optimal care.The improvement of staging with high-resolution imaging has allowed more selective treatments,optimising survival outcomes.The next step is to identify biomarkers that can inform clinicians of expected prognosis and offer the most beneficial treatment,while reducing unnecessary morbidity for the patient.The search for biomarkers in CRC has been of significant interest,with questions remaining on their impact and applicability.The study of biomarkers can be broadly divided into metabolic,molecular,micro RNA,epithelial-to-mesenchymal-transition(EMT),and imaging classes.Although numerous molecules have claimed to impact prognosis and treatment,their clinical application has been limited.Furthermore,routine testing of prognostic markers with no demonstrable influence on response to treatment is a questionable practice,as it increases cost and can adversely affect expectations of treatment.In this review we focus on recent developments and emerging biomarkers with potential utility for clinical translation in CRC.We examine and critically appraise novel imaging and molecular-based approaches; evaluate the promising array of micro RNAs,analyze metabolic profiles,and highlight key findings for biomarker potential in the EMT pathway.

快速转诊的大量增加改善了英国肠癌患者的预后吗?

Michael Thompson及其同事认为,需要更精确的风险分层以确保及时诊断肠癌,同时避免不必要的检查。英国卫生部为了提高肠癌患者的生存率,制定了全科医生转诊指南和公众宣传活动的政策,这些政策增加了紧急转诊到医院的人数,还导致了并无明显临床获益的不必要肠镜检查和CT结肠造影。