BackgroundVery little is known about the relationship between non-sickle cell anemia and stroke. The purpose of this study is to evaluate the association of iron-deficiency anemia (IDA) with stroke based on a nationwide coverage database in Taiwan.MethodsThe case-control study subjects were obtained from the Taiwanese Longitudinal Health Insurance Database 2000. We included 51,093 subjects with stroke as cases and randomly selected 153,279 controls (3 controls per case) in this study.Separate conditional logistic regression analyses were used to calculate the odds ratio (OR) for having been previously diagnosed with IDA between cases and controls.We further analyzed the association between stroke and IDA by stroke subtype. ResultsResults showed that 3,685 study subjects (1.81%) had been diagnosed with IDA prior to the index date; of those subjects, 1,268 (2.48%) were cases and 2,417 (1.58%) were controls (p<0.001). Conditional logistic regression shows that the OR of having previously received an IDA diagnosis among cases was 1.49 (95% CI: 1.39~1.60; p < 0.01) that of controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, atrial fibrillation, heart failure, hyperlipidemia, tobacco use disorder, and alcohol abuse/alcohol dependency syndrome. Furthermore, the adjusted OR of prior IDA for cases with ischemic stroke was found to be 1.45 (95% CI: 1.34~1.58) compared to controls. However, we did not find any significant relationship between IDA and subarachnoid/intracerebral hemorrhage even adjusting for other confounding factors (OR=1.17, 95% CI=0.97~1.40). ConclusionThere is a significant association between prior IDA and ischemic stroke.

Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of and mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (∼60%) peripheral blood Treg cells express CCR6, and CCR6 Treg cells exhibit an activated effector/memory phenotype. In contrast, a significant portion (>30%) of CCR6 Treg cells were found to be CD45RA naive Treg cells. Compared to CCR6 naive or memory Treg cells, CCR6 Treg cells exhibit stronger suppressive activity and display higher FOXP3 expression along with lower methylation at the Treg-specific demethylated region of the gene. This predominance of CCR6 Treg cells was also found in the draining lymph nodes and tumor-infiltrating lymphocytes of OSCC patients with early or late clinical staging. Moreover, CCR6 Treg cells isolated from tumor-infiltrating lymphocytes or draining lymph nodes maintained similar phenotypic and suppressive characteristics ex vivo as did their counterparts isolated from peripheral blood. These results suggest that CCR6 marks activated effector or memory Treg phenotypes with superior suppressive activity in humans.

CD8+ T cells play important roles in anti-tumor immunity but distribution profile or functional characteristics of effector memory subsets during tumor progression are unclear. We found that, in oral squamous carcinoma patients, circulating CD8+ T cell pools skewed toward effector memory subsets with the distribution frequency of CCR7−CD45RA−CD8+ T cells and CCR7− CD45RA+CD8+ T cells negatively correlated with each other. A significantly higher frequency of CD127lo CCR7−CD45RA−CD8+ T cells or CCR7−CD45RA+CD8+ T cells among total CD8+ T cells was found in peripheral blood or tumor infiltrating lymphocytes, but not in regional lymph nodes. The CD127hi CCR7−CD45RA−CD8+ T cells or CCR7−CD45RA+CD8+ T cells maintained significantly higher IFN-γ, IL-2 productivity and ex vivo proliferative capacity, while the CD127lo CCR7−CD45RA−CD8+ T cells or CCR7−CD45RA+CD8+ T cells exhibited higher granzyme B productivity and susceptibility to activation induced cell death. A higher ratio of CCR7−CD45RA+CD8+ T cells to CCR7−CD45RA−CD8+ T cells was associated with advanced cancer staging and poor differentiation of tumor cells. Therefore, the CD127lo CCR7−CD45RA−CD8+ T cells and CCR7−CD45RA+CD8+ T cells are functionally similar CD8+ T cell subsets which exhibit late differentiated effector phenotypes and the shift of peripheral CD8+ effector memory balance toward CCR7−CD45RA+CD8+ T cells is associated with OSCC progression.