One hundred sixty-eight Holstein steer calves (133.4 ± 7.9 kg) were used to evaluate the influence of virginiamycin (VM) supplementation on cattle growth performance and liver abscess incidence, and the effect of feeding 100% vs. 87% of metabolizable protein (MP) requirements during the initial 112 d on growth performance, efficiency of energy utilization, and carcass characteristics. Steers were balanced by weight and assigned to 28 pens (6 steers/pen). During the initial 112-d feeding period, dietary treatments consisted of two levels of MP (100% vs. 87% of expected requirements) supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement. There were no VM × MP supplementation interactions (P ≥ 0.14) on any of the parameters measured in both experiments. Calf-fed Holstein steers supplemented with VM increased (P ≤ 0.03) overall average daily gain (ADG), feed efficiency (G:F), observed/expected net energy (NE) values for maintenance and gain, and final body weight (BW). Cattle fed VM also increased (P ≤ 0.04) carcass weight, dressing percent, and longissimus muscle area. However, there was no effect (P ≥ 0.22) of VM supplementation on any other carcass characteristics. Calf-fed Holstein steers fed 100% MP requirements during the initial 112-d feeding period had greater (P ≤ 0.02) ADG, G:F, observed/expected NE values for maintenance and gain, and live BW compared with steers fed 87% of the expected MP requirements. However, there was no effect (P ≥ 0.17) of MP supply during the initial 112-d period on overall (342 d) growth performance measurements. The incidence of liver abscesses was low (averaging 7.7%) and not affected by dietary treatments. We conclude that, independent of MP supplies, supplemental VM enhances overall growth performance and efficiency of energy utilization of calf-fed Holstein steers.

Evaluation of the effects of feeding NutraGen supplement (NutraGen, NTG; Phibro Animal Health, Teaneck, NJ, USA) on growth performance, energetic efficiency, carcass characteristcs, and characteristics of digestion in calf-fed Holstein steers fed a conventional growing-finishing diet. Trial 1 evaluated growth performance, dietary energetics and carcass characteristics. Two hundred Holstein steer calves (134 ± 5 kg) were blocked by initial body weight (BW) and randomly assigned to 40 pens (5 steers/pen). Dietary treatments consisted of a steam-flaked corn-based growing-finishing diet supplemented with 0, 0.2, 0.4, or 0.6% NTG (DM basis). In trial 2, four Holstein steers (170 ±6 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square experiment to evaluate digestibility and ruminal characteristics using the treatments from trial 1. Compared to non-supplemented cattle, NTG increased BW (2.0%, P = 0.02) and tended to increase ADG (3.6%, P = 0.07) during the initial 56 d period. However, there were no treatment effects on overall growth performance and efficiency of dietary energy utilization after the first 56 days (P > 0.10). Supplementation of NTG increased (linear effect; P ≤ 0.03) longissimus muscle area and kidney, pelvic, and heart fat. There was no effect (P ≥ 0.05) of NTG supplementation on other carcass characteristics, liver abscess incidence, or liver abscess scars. Supplementation decreased the molar proportion of ruminal propionate (P = 0.05) and tended to increase acetate:propionate molar ratio (P = 0.09). However, there was no effect of NTG supplementation on ruminal and total tract diet digestion. NTG increased performance of Holstein steers during the first 56 d on feed in the feedlot. In addition, the steers had an increase in KPH fat and LM area, indicating that the additive induced change in metabolism of the steers.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1⁺PD1^loCD62L^- CD8⁺ T cells. These IFNγ-producing effector CD8⁺ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)⁺CD206^- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8⁺ T cells.