Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC

Pain Management in People with Inflammatory Arthritis: British Society for Rheumatology Guideline Scope.

Pain is a common symptom in people with inflammatory arthritis (IA), which has far-reachingimpacts on their lives. Recent electronic health record studies demonstrate that UK-based paincare in people with IA commonly involves the prescribing of long-term opioids andgabapentinoids, despite an absence of trial evidence for their efficacy. Patient surveys suggestthat non-pharmacological pain management is underused. A UK-specific guideline on painmanagement for people with IA is required to resolve this. This scoping document outlines thecontext and prioritised clinical questions for the first British Society for Rheumatology (BSR)guideline on pain management for people with IA. The guideline aims to provide evidence-based recommendations on how pain can be best managed in people with IA (including itsassessment, and pharmacological and non-pharmacological treatments), ensuring that peoplewith IA in the UK are offered evidence-based pain management strategies. The guideline is forhealthcare professionals involved in the care of people with IA of all ages and genders, peoplewith IA and their families and carers, NHS managers and healthcare commissioners, and otherrelevant stakeholders such as patient organisations. It will be developed using the methodsoutlined in the BSR’s “Creating Clinical Guidelines” protocol

Proteomic biomarkers of type 2 diabetes mellitus risk in women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are at increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In this study, we attempted to list the proteomic biomarkers of PCOS and T2DM that have been published in the literature so far. We identified eight common biomarkers that were differentially expressed in both women with PCOS and T2DM when compared with healthy controls. These include pyruvate kinase M1/M2, apolipoprotein A-I, albumin, peroxiredoxin 2, annexin A2, alpha-1-B-glycoprotein, flotillin-1 and haptoglobin. These biomarkers could help improve our understanding of the links between PCOS and T2DM and could be potentially used to identify subgroups of women with PCOS at increased risk of T2DM. More studies are required to further evaluate the role these biomarkers play in women with PCOS and T2DM. European Journal of Endocrinology 168 R33-R4

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC