SLAMF6 deficiency augments tumor killing and skews toward an effector phenotype revealing it as a novel T cell checkpoint
ELIFE
Authors: Hajaj, Emma; Eisenberg, Galit; Klein, Shiri; Frankenburg, Shoshana; Merims, Sharon; Ben David, Inna; Eisenhaure, Thomas; Henrickson, Sarah E.; Villani, Alexandra Chloe; Hacohen, Nir; Abudi, Nathalie; Abramovich, Rinat; Cohen, Jonathan E.; Peretz, Tamar; Veillette, Andre; Lotem, Michal
Abstract
SLAMF6 is a homotypic receptor of the Ig-superfamily whose exact role in immune modulation has remained elusive. Its constitutive expression on resting and activated T cells precludes it from being a bona fide exhaustion marker. By breeding Pmel-1 mice with SLAMF6 -/- mice, we generated donors for T cells lacking SLAMF6 and expressing a transgenic TCR for gp100melanoma antigen. Activated Pmel-1xSLAMF6 -/- CD8+ T cells displayed improved polyfunctionality and strong tumor cytolysis. T-bet was the dominant transcription factor in Pmel-1 x SLAMF6 -/- cells, and upon activation, they acquired an effector-memory phenotype. Adoptive transfer of Pmel-1 x SLAMF6 -/- T cells to melanoma-bearing mice resulted in lasting tumor regression in contrast to temporary responses achieved with Pmel-1 T cells. LAG-3 expression was elevated in the SLAMF6 -/- cells, and the addition of the LAG-3-blocking antibody to the adoptive transfer protocol improved the SLAMF6 -/- T cells and expedited the antitumor response even further. The results from this study support the notion that SLAMF6 is an inhibitory immune receptor whose absence enables powerful CD8+ T cells to eradicate tumors.
The effects of pretransportation or arrival meloxicam administration to calves entering the feedlot on morbidity, biomarkers, performance, and carcass characteristics
TRANSLATIONAL ANIMAL SCIENCE
Authors: Van Engen, Nicholas K.; Engelken, Terry J.; Lockard, Caleb G.; Lakritz, Jeffery; Cernicchiaro, Natalia; Wilson, Blake K.; Krehbiel, Clint R.; Coetzee, Johann F.
Abstract
The objective of this trial was to investigate the effects of using meloxicam as a pretransport or on arrival therapeutic on disease outcomes of bovine respiratory disease (BRD), biomarker outcomes associated with BRD, performance characteristics over the first 42 d on feed, and carcass traits at harvest in cross bred beef cattle. Multisourced, crossbred steer calves (n = 168) consisting of mainly British and British-Continental breeds were purchased from an auction market in central Missouri. Calves were processed prior to transportation and again upon feedlot arrival. Animals were randomized to 3 separate treatments: pretransport meloxicam (PMEL), arrival meloxicam (AMEL), and a control group receiving inactive excipient (CONT). Dosing at 1 mg/kg on weighted averaged administered per os. Animals were weighed and blood was collected pre- and post-transport. Haptoglobin (Hp)-matrix metaloproteinase (MMP)-9 complex, cortisol, and substance P were quantified. Weights were taken again at 42 d and at harvest. Clinical signs of BRD were monitored using indicators of depression, appetite, respiration, and temperature that qualified the animals for treatment. Harvest parameters were collected using a standardized United States Department of Agriculture grading system for quality grade and yield grade. Meloxicam did not have a significant effect on BRD morbidity over the course of the study and there was no significant effect on performance characteristics at 42 d (P > 0.10). Of the calves that did succumb to BRD, no significant differences were found in severity of disease (P > 0.10). Concentrations of substance P and HpMMP-9, were increased on arrival (P 0.05) however no significant treatment effect or interaction were found between AMEL, PMEL, CONT, or across different levels of biomarkers (P > 0.10). Meloxicam use prior to or on arrival does not mitigate disease or improve performance during the feeding period.