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Background: People experiencing homelessness are more likely to experience poor health with physical functioning deficits and frailty commonly reported. It is not well known how strategies to target physical functioning deficits and frailty work in practice in this group. The primary aim of this study was to explore the feasibility of an exercise intervention with protein supplementation to target physical functioning and frailty in people experiencing homelessness evaluated by recruitment and retention rates, adherence to the exercise sessions and protein supplement, adverse effects, programme feedback and characteristics of non-returners, sporadic and frequent attenders. The secondary aim was to evaluate changes in effectiveness outcomes of grip strength, muscle mass, lower extremity physical function, pain, frailty, and risk of malnutrition. Method: This prospective single-arm study evaluated the feasibility of a 16-week rolling, low-threshold, 'drop-in' once weekly exercise programme with protein supplementation. The main recruitment site was a day-service centre for people who are homeless. Feasibility was assessed by the recruitment and retention rates, adherence to the exercise sessions and protein supplement as well as adverse effects, programme feedback and evaluation of characteristics of non-returners, sporadic (≤50% of available sessions) and frequent attenders (≥50% of available sessions). Effectiveness outcomes included pain (Visual Analogue Scale), physical functioning and performance (hand-grip dynamometry, limb circumference, the Short Physical Performance Battery), frailty (SHARE-FI and Clinical Frailty Scale) and nutritional status (Mini Nutritional Assessment). Results: Thirty-one participants were recruited mean (SD) age 45(16) years. There was a recruitment rate of a median (IQR) of 2(1–3) new participants per week. The retention rate was 45% (n = 14) to the main recruitment site. Adherence to the exercise sessions and nutritional intervention was 90% and 100% respectively. Three adverse events were recorded during 74 interventions over the 16-week programme. The acceptability of the programme was highlighted in participant feedback. Characteristics of frequent returners (≥50%) were older age, female, more stably housed and more stable in addiction. The programme did not induce any changes in effectiveness outcomes. Conclusion: The feasibility of this programme was demonstrated. Overall, the programme was well received with higher retention rates in older participants, females, those more stably housed and those stable in addiction. A higher powered, more intense programme is needed to demonstrate programme effectiveness. [ABSTRACT FROM AUTHOR]

Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

Objectives Cancer patient outcomes and selection for novel therapies are heavily influenced by the immune contexture of the tumor microenvironment. Esophageal cancer is associated with poor outcomes. In contrast to colorectal cancer, where the immunoscore is increasingly used in prognostic staging, little is known about the immune cell populations in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC), and their clinical significance. Methods Tissue microarrays were constructed from resected tumor tissue of 72 EAC patients and 23 SCC patients. Immunohistochemical staining of CD3, CD8, CD56, CD68, CD45RO, CD69, IFN-γ, IL-10, IL-4, IL-17, TGF-β, FOXP3 and CD107a was performed. Positivity was examined in both the stromal and epithelial compartments. Statistical analysis was performed to identify differences in immune cell infiltration and functional phenotypes between cancer subtypes and tissue compartments. Results This study identified that esophageal tumors are enriched with CD45RO+ and CD8+ cells and such positivity is significantly higher in SCC compared with EAC. Furthermore, the expression of CD45RO positively correlates with that of CD8 within the tumors of both patient cohorts, suggesting a dominance of memory cytotoxic T cells. This is supported by strong positivity of degranulation marker CD107a in the stromal compartment of EAC and SCC tumors. Cytokine staining revealed a mixed pro- and anti-inflammatory profile within EAC tumors. Conclusions Esophageal tumors are enriched with memory cytotoxic T cells. Applying these measurements to a larger cohort will ascertain the clinical utility of assessing specific lymphocyte infiltrates in EAC and SCC tumors with regards to future immunotherapy use, patient prognosis and outcomes. [ABSTRACT FROM AUTHOR]

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maINTenance of the CX3CR1NEG CD8+ T cell populations. [ABSTRACT FROM AUTHOR]

There is increasing recognition of the impact of being overweight and obese on the development of cancers at diverse sites including the gastrointestinal tract. Large epidemiological studies indicate that up to 14% of tumours may be related to obesity. Pathophysiological mechanisms underpinning this association are not well understood and so are discussed in this review. [ABSTRACT FROM PUBLISHER]

This paper presents emerging evidence linking visceral adiposity and the metabolic syndrome (MetSyn) with carcinogenesis. The link between obesity and cancer has been clearly identified in a multitude of robust epidemiological studies. Research is now focusing on the role of visceral adipose tissue in carcinogenesis; as it is recognised as an important metabolic tissue that secretes factors that systemically alter the immunological, metabolic and endocrine milieu. Excess visceral adipose tissue gives rise to a state of chronic systemic inflammation with associated insulin resistance and dysmetabolism, collectively known as the MetSyn. Prospective cohort studies have shown associations between visceral adiposity, the MetSyn and increased risk of breast cancer, colorectal cancer and oesophageal adenocarcinoma. Furthermore, visceral adiposity and the MetSyn have been associated with increased tumour progression and reduced survival. The mechanisms by which visceral adiposity and the MetSyn are thought to promote tumorigenesis are manifold. These include alterations in adipokine secretion and cell signalling pathways. In addition, hyperinsulinaemia, subsequent insulin resistance and stimulation of the insulin-like growth factor-1 axis have all been linked with visceral adiposity and promote tumour progression. Furthermore, the abundance of inflammatory cells in visceral adipose tissue, including macrophages and T-cells, create systemic inflammation and a pro-tumorigenic environment. It is clear from current research that excess visceral adiposity and associated dysmetabolism play a central role in the pathogenesis of certain cancer types. Further research is required to elucidate the exact mechanisms at play and identify potential targets for intervention. [ABSTRACT FROM PUBLISHER]

The omentum is enriched with pro-inflammatory effector memory CD8 + T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8 + T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8 + T cells expressing intermediate levels (CX3CR1 INT ) are defined as peripheral memory, those expressing the highest levels (CX3CR1 HI ) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1 NEG ) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8 + T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8 + T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8 + T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1 INT and CX3CR1 HI CD8 + T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8 + T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1 NEG CD8 + T cells express higher levels of L-selectin than CX3CR1 INT CD8 + T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1 INT CD8 + T cells to a CX3CR1 NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8 + T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1 NEG CD8 + T cell populations.