Optimising multiplex immunofluorescence staining for characterising the tumour immune micro-environment.

Exploring the tumour microenvironment provides insight into the unique interaction between the host and tumour. Ultimately, its study improves understanding of how an individual mounts and achieves an anti-tumour immune response. In the context of colorectal cancer, immune biomarkers within the tumour microenvironment outperform traditional histopathological staging in predicting disease recurrence.

Circulating tumour DNA in colorectal cancer management.

Circulating tumour DNA analysis can be performed using two opposing paradigms: tumour-informed and tumour-agnostic approaches. The first requires sequencing data from the primary tumour sample to identify tumour DNA in circulation, whereas the latter occurs without previous primary tumour genetic profiling. Several preanalytical and laboratory considerations need to be taken into account before proceeding with in-house circulating tumour DNA analysis.

Fusobacterium nucleatum and Bacteroides fragilis detection in colorectal tumours: Optimal target site and correlation with total bacterial load.

Background: Mucosal infiltration by certain bacterial species may contribute to the development and progression of colorectal cancer (CRC). There is considerable variation in reported detection rates in human CRC samples and the extent to which bacterial infiltration varies across regions of the primary tumour is unknown. This study aimed to determine if there is an optimal site for bacterial detection within CRC tumours.

PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

Background: The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c DC co-expressing the immunoinhibitory molecule PD-L1 and their spatial relationship with CD8 T-cells in patients treated for stage III colon cancer.

The Prognostic and Predictive Value of SOX2 Cell Densities in Patients Treated for Colorectal Cancer.

SOX2 (sex-determining region-Y homeobox-2) is a transcription factor essential for the maintenance of pluripotency and is also associated with stem-cell-like properties in preclinical cancer models. Our previous study on a cohort of stage III colon cancer patients demonstrated high SOX2 cell densities were associated with poor prognosis. However, most patients were treated with adjuvant chemotherapy so the prognostic value of SOX2 could not be assessed independently from its value as a predictive marker for non-response to chemotherapy.

Optimisation of multiplex immunofluorescence for a non-spectral fluorescence scanning system.

The use of multi-colour immunofluorescence (IF) for immunophenotyping in formalin-fixed paraffin-embedded tissue sections is gaining popularity worldwide. This technique allows for the simultaneous detection of multiple markers on the same tissue section, thereby yielding more complex information than is possible by chromogenic immunohistochemistry (IHC). However, many commercially-available multiplex IF kits are designed for use in conjunction with a multispectral imaging system, to which many research groups have limited access.

Expression of PD-L1 and SOX2 during rectal tumourigenesis: Potential mechanisms for immune escape and tumour cell invasion.

Immunoediting is defined as a process whereby tumour cells develop the capacity to escape immune cell recognition. Accumulating evidence suggests that cancer stem-like cells (CSCs) have an enhanced capacity to interact with the immune system. The expression of CSCs and immune cell-associated markers has been demonstrated to change with disease progression from premalignant lesions to invasive cancer.

Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response.

Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy.

Neoadjuvant chemoradiotherapy for rectal cancer: how important is tumour regression?

Background: Pathological complete response following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer is associated with reduced local recurrence and improved long-term outcome. However, the prognostic value of a partial response, or of tumour regression in patients with metastatic disease, is less clear.

Methods: We present a single-centre cohort study of 205 patients with stage II-IV rectal cancer treated with surgery and neoadjuvant CRT between 2006 and 2013.

Peripheral CD8(+) T cell proliferation is prognostic for patients with advanced thoracic malignancies.

There is a complex interplay between the immune system and a developing tumor that is manifest in the way that the balance of T cell subsets in the local tumor environment reflects clinical outcome. Tumor infiltration by CD8(+) T cells and regulatory T cells (Treg) is associated with improved and reduced survival, respectively, in many cancer types. However, little is known of the prognostic value of immunological parameters measured in peripheral blood.

Disease activity, smoking, and reproductive-related predictors of poor prognosis in patients with very early inflammatory polyarthritis.

Objective: To identify disease activity, smoking, and reproductive-related predictors of a poor prognosis in patients with very early inflammatory polyarthritis (IP).

Methods: Patients with very early IP (symptom duration 4-11 weeks) included in our study were participants in the STIVEA (Steroids In Very Early Arthritis) randomized placebo-controlled trial. At baseline, disease-related variables were measured and patients were asked to complete a questionnaire covering smoking status and reproductive questions.

A novel prognostic model for malignant mesothelioma incorporating quantitative FDG-PET imaging with clinical parameters.

Purpose: Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease.

Experimental Design: Patients with malignant pleural mesothelioma underwent helical thoracoabdominal computed tomography and FDG-PET scans at baseline.

Why do patients with inflammatory arthritis often score states "worse than death" on the EQ-5D? An Investigation of the EQ-5D classification system.

Objective: Using inflammatory arthritis patients as an example, we investigate EuroQol-5D (EQ-5D) profiles resulting in states worse than death (WTD), and the heath status of patients occupying these states.

Methods: Baseline data from two UK trials were used that reflected the range of arthritis states/severity found in routine practice. EQ-5D profiles resulting in negative valuations (i.

The genetic predisposition to produce high levels of TGF-beta1 impacts on the severity of eclampsia/pre-eclampsia.

Objectives: To investigate the hypothesis that women who are genetically programmed to produce higher levels of transforming growth factor-beta 1 are more likely to develop severe eclampsia/pre-eclampsia.

Design: Case-control study.

Methods: Blood samples from women whose pregnancy was complicated by eclampsia (n=37) or pre-eclampsia (n=49) and healthy controls (n=86) were analyzed for the presence of polymorphisms at codons 10 and 25 of the transforming growth factor-beta 1 gene.

Association between novel GM-CSF gene polymorphisms and the frequency and severity of atopic dermatitis.

Background: Genetic factors are known to be important in determining an individual's predisposition to atopic dermatitis. The specific genes that are clinically important in this process are still largely unknown.

Objective: Because dendritic cells initiate immune responses and thus are critical to the priming of an individual to potential allergens, we hypothesized that genetic factors controlling the activity of these cells determine an individual's propensity to atopic dermatitis.