Quality of CD8+ T cell immunity evoked in lymph nodes is compartmentalized by route of antigen transport and functional in tumor context.

Revealing the mechanisms that underlie the expansion of antitumor CD8+ T cells that are associated with improved clinical outcomes is critical to improving immunotherapeutic management of melanoma. How the lymphatic system, which orchestrates the complex sensing of antigen by lymphocytes to mount an adaptive immune response, facilitates this response in the context of malignancy is incompletely understood. To delineate the effects of lymphatic transport and tumor-induced lymphatic and lymph node (LN) remodeling on the elicitation of CD8+ T cell immunity within LNs, we designed a suite of nanoscale biomaterial tools enabling the quantification of antigen access and presentation within the LN and resulting influence on T cell functions. The expansion of antigen-specific stem-like and cytotoxic CD8+ T cell pools was revealed to be sensitive to the mechanism of lymphatic transport to LNs, demonstrating the potential for nanoengineering strategies targeting LNs to optimize cancer immunotherapy in eliciting antitumor CD8+ T cell immunity.

Passive cooling during transport of asphyxiated term newborns.

OBJECTIVE: To evaluate the efficacy and safety of passive cooling during transport of asphyxiated newborns. STUDY DESIGN: Retrospective medical record review of newborns with perinatal asphyxia transported for hypothermia between July 2007 and June 2010. RESULT: Of 43 newborns transported, 27 were passively cooled without significant adverse events. Twenty (74%) passively cooled newborns arrived with temperature between 32.5 and 34.5 °C. One newborn arrived with a temperature <32.5, and 6 (22%) had temperatures >34.5 °C. Time from birth to hypothermia was significantly shorter among passively cooled newborns compared with newborns not cooled (215 vs 327 min, P<0.01), even though time from birth to admission to Boston Children's Hospital was similar (252 vs 259 min, P=0.77). Time from birth to admission was the only significant predictor of increased time to reach target temperature (P=0.001). CONCLUSION: Exclusive passive cooling achieves significantly earlier initiation of effective hypothermia for asphyxiated newborns but should not delay transport for active cooling.