LIGHT, a ligand for the lymphotoxin-β receptor, establishes lymphoid-like tissues inside tumor sites and recruits naïve T cells into the tumor. However, whether these infiltrating T cells are specific for tumor antigens is not known. We hypothesized that therapy with LIGHT can expand functional tumor-specific CD8 + T cells that can be boosted using HPV16E6E7-Venezuelan equine encephalitis virus replicon particles (HPV16-VRP) and that this combined therapy can eradicate human papillomavirus 16 (HPV16)-induced tumors. Our data show that forced expression of LIGHT in tumors results in an increase in expression of IFNγ and chemoattractant cytokines such as interleukin-1a, MIG, and macrophage inflammatory protein-2 within the tumor and that this tumor microenvironment correlates with an increase in frequency of tumor-infiltrating CD8 + T cells.Forced expression of LIGHT also results in the expansion of functional T cells that recognize multiple tumor antigens, including HPV16 E7, and these T cells prevent the outgrowth of tumors on secondary challenge. Subsequent boosting of E7-specific T cells by vaccination with HPV16-VRP significantly increases their frequency in both the periphery and the tumor and leads to the eradication of large well-established tumors, for which either treatment alone is not successful. These data establish the safety of Ad-LIGHT as a therapeutic intervention in preclinical studies and suggest that patients with HPV16 + tumors may benefit from combined immunotherapy with LIGHT and antigen-specific vaccination. Cancer Res; 70(10); 3955-64. ©2010 AACR.

No abstract

Geriatric trauma has historically been associated with poor outcomes, particularly in the setting of severe polytrauma. Although geriatric trauma protocols are common, there are limited data on their impact in patients with high injury severity. In this study, we sought to investigate the impact of a geriatric injury protocol on outcomes in patients with severe trauma acuity. Ninety-eight geriatric patients (age ≥65) admitted to our trauma center with injury severity scores (ISS) ≥15 comprised the study cohort. The mean age was 75 ± 7.7 yrs. The mean ISS was 25 ± 9.2, and the mean geriatric trauma outcome score was 150 ± 3. Mortality was 17 per cent and 70 per cent were due to central nervous system injury. When patients with nonsurvivable injuries or advanced directives resulting in early care withdrawal were excluded, the mortality was 6 per cent. Extremes of age did not impact mortality [(>80 years, 21%) vs (65–79, 16%, P = 0.5)]. Most patients (53%) were discharged home. The application of our geriatric trauma protocol led to favorable results despite high injury acuity. These data suggest that even at the extremes of age, a large percentage of patients can be expected to survive. A prospective validation of these findings is warranted.