No abstract

Mesenchymal stem cells (MSCs) represent an important cellular constituent of the tumor microenvironment, which along with tumor cells themselves, serve to regulate protective immune responses in support of progressive disease. We report that tumor MSCs prevent the ability of dendritic cells (DC) to promote naïve CD4(+) and CD8(+) T cell expansion, interferon gamma secretion and cytotoxicity against tumor cells, which are critical to immune-mediated tumor eradication. Notably, tumor MSCs fail to prevent DC-mediated early T cell activation events or the ability of responder T cells to produce IL-2. The immunoregulatory activity of tumor MSCs is IL-10- and STAT3-dependent, with STAT3 repressing DC expression of cystathionase, a critical enzyme that converts methionine-to-cysteine. Under cysteine-deficient priming conditions, naïve T cells exhibit defective cellular metabolism and proliferation. Bioinformatics analyses as well as in vitro observations suggest that STAT3 may directly bind to a GAS-like motif within the cystathionase promoter (-269 to -261) leading to IL-10-STAT3 mediated repression of cystathionase gene transcription. Our collective results provide evidence for a novel mechanism of tumor MSC-mediated T cell inhibition within tumor microenvironment.

Background Parent and teen health literacies (HL) are employed as teens with chronic illnesses transition to health self-management and the adult health system. This study explores the relationships between parent and teen HL. Methods Teens ages 12-18 with chronic conditions and their parents, sampled from a pediatric Medicaid ACO, completed an interview assessing HL and self-reported competence with written and numeric health information. Rates of teen and parent HL, degree of concordance, and relationship between concordance and teen-reported competence with health materials were measured. Results Half (52%) of teens had adequate HL. 62% of teens reported competence with written health materials and 69% with numeric information. Correlation between parent and teen HL was modest but significant (phi=0.13; p=0.03). 47% of parent-teen dyads were concordant for adequate HL while 10% were concordant inadequate. Adequate teen HL was associated with parental adequate HL and parental education. Discordance was associated with self-reported competence with written material and numeric material. Conclusion Over half of parent-teen dyads had at least one member with less than adequate health literacy and parent-teen HL concordance were associated with teen perception of health literacy. These findings support the consideration of both independent and dyad HL levels in adolescent care.

Health literacy (HL) research among Hispanics currently focuses on individuals with limited English proficiency but impacts of HL on healthcare outcomes among other English language proficiency groups is relatively unknown. Regression models assessed associations between HL and healthcare outcomes for Hispanics overall (n = 4013) and for proficiency level sub-populations using the 2007 Pew Hispanic Health Survey. Overall, Hispanics with adequate HL percieved US medical care as "excellent," were more satisfied with their doctor's help, and reported "excellent" overall health. In the sub-population analysis, "excellent" perception of US healthcare was associated with HL among the Spanish and English dominant groups. Among bilinguals, adequate HL was associated with decreased use of traditional medicine. The effect of adequate HL varied within English proficiency groups. HL research that focuses only on Spanish dominant speakers can exclude a substantial percentage of English proficient or bilingual populations who have low HL.