Single-Cell Immune Competency Signatures Associate with Survival in Phase II GVAX and CRS-207 Randomized Studies in Patients with Metastatic Pancreatic Cancer.

The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (N = 38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8+CD45RO-CCR7-CD57+ cells and a lower abundance of CD14+CD33+CD85j+ cells had improved overall survival [median overall survival, range (days) 271, 43-1,247] compared with patients with a lower abundance of CD8+CD45RO-CCR7-CD57+ cells and higher abundance of CD14+CD33+CD85j+ cells (77, 24-1,247 days; P = 0.0442). The results from this prospective-retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

Relationship Between Amino Acid and Energy Intake and Long-Term Growth and Neurodevelopmental Outcomes in Very Low Birth Weight Infants.

BACKGROUND: Inadequate nutrition may contribute to adverse neurodevelopmental and growth outcomes in very low birth weight (VLBW) infants. MATERIALS AND METHODS: A retrospective cohort study was conducted of infants born weighing <1250 g between 2009 and 2010 in a tertiary neonatal intensive care unit. The aim was to investigate whether there was a correlation between the amount of amino acid and calories received in the first 4 weeks of life and neurodevelopment and growth at 2 years. RESULTS: Parenteral amino acid intake in week 2 of life correlated with higher language and motor scores on the 2-year Bayley Scales of Infant and Toddler Development Third Edition (Bayley III). Conversely, higher total amino acid intake during week 1 of life (≥1.5 g/kg/d) was associated with a shorter duration of hospitalization, shorter intensive care stay, fewer days receiving mechanical ventilation, fewer days receiving supplemental oxygen, and a lower incidence of chronic lung disease (CLD). Higher caloric intake in the first 4 weeks correlated strongly with shorter duration of hospitalization, shorter intensive care stay, fewer days on the ventilator, and fewer days receiving supplemental oxygen. In patients with CLD, week 1 and 2 parenteral and total amino acid intake correlated with higher cognitive and motor scores on the Bayley III at 2 years old. Weeks 1-4 amino acid and calorie intake correlated with fewer days on the ventilator, fewer days of supplemental oxygen, and fewer days of hospitalization. CONCLUSION: Amino acid intake within the first weeks of life correlated positively with neurodevelopmental outcomes at 2 years, and patients with CLD were found to be particularly at risk. Caloric intake may affect protein accretion.