In humans, T cells differentiate in thymus and B cells develop in bone marrow (BM), but the natural killer (NK) precursor cell(s) and site(s) of NK development are unclear. The CD56bright NK subset predominates in lymph nodes (LN) and produces abundant cytokines compared to the cytolytic CD56dim NK cell that predominates in blood. Here, we identify a novel CD34dimCD45RA(+) hematopoietic precursor cell (HPC) that is integrin alpha4beta7bright. CD34dimCD45RA(+)beta7bright HPCs constitute <1% of BM CD34(+) HPCs and approximately 6% of blood CD34(+) HPCs, but >95% of LN CD34(+) HPCs. They reside in the parafollicular T cell regions of LN with CD56bright NK cells, and when stimulated by IL-15, IL-2, or activated LN T cells, they become CD56bright NK cells. The data identify a new NK precursor and support a model of human NK development in which BM-derived CD34dimCD45RA(+)beta7bright HPCs reside in LN where endogenous cytokines drive their differentiation to CD56bright NK cells in vivo.

The California Cancer Registry was analyzed for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance types. Survival analyses were performed for 72,452 cases to determine the prognostic significance of racial and socioeconomic factors. Black race, low SES, and Medicaid insurance portend poorer outcomes. These findings reflect a multifaceted socioeconomic and public health conundrum.Purpose: To examine the California Cancer Registry (CCR) for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance in California patients. Patients and Methods:The CCR was queried for bladder cancer cases in California from 1988 to 2012. The primary outcome was disease-specific survival (DSS), defined as the time interval from date of diagnosis to date of death from bladder cancer. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors.Results: A total of 72,452 cases were included (74.5% men, 25.5% women). The median age was 72 years (range, 18-109 years). The racial distribution among the patients was 81% white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% from other races. In black patients, tumors presented more frequently with advanced stage and high grade. Medicaid patients tended to be younger and had more advanced-stage, higher-grade tumors compared to patients with Medicare or managed care (P < .0001). Kaplan-Meier analysis demonstrated significantly poorer 5-year DSS in black, low SES, and Medicaid patients (P < .0001). When controlling for stage, grade, age, and gender, multivariate analysis revealed that black race (DSS hazard ratio = 1.295; 95% confidence interval, 1.212-1.384), low SES (DSS hazard ratio = 1.325; 95% confidence interval, 1.259-1.395), and Medicaid insurance (DSS hazard ratio = 1.349; 95% confidence interval, 1.246-1.460) were independent prognostic factors (P < .0001).

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