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Recent interest has focused on the function of gamma delta + T cells in immune responses. However, their role in allogeneic bone marrow transplantation (BMT) remains undefined. We report on a group of 43 leukemia patients who survived for at least 100 days following transplantation using partially HLA-mismatched grafts from related donors that were T cell depleted with the anti-TCR alpha beta monoclonal antibody T10B9.1A-31 and complement. Ten patients (23.2%) were found to have an increased (> or = 10%) proportion of gamma delta + T cells in the peripheral blood at 60-270 days after BMT. All of these patients remain alive, and 9 (90% of patients with > or = 10% gamma delta + cells) are free of disease at 2.5 years compared with a disease-free survival probability of 31% among patients with a normal proportion and concentration of gamma delta + T cells. No other factor was found to be independently associated with improved survival in these patients. These data suggest a possible association between an increase in the percentage and number of gamma delta + T cells and improved disease-free survival following transplantation from a partially mismatched related donor.

Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor highly expressed in the liver and modulating HDL metabolism. Hepatitis C virus (HCV) is able to directly interact with SR-BI and requires this receptor to efficiently enter into hepatocytes to establish productive infection. A complex interplay between lipoproteins, SR-BI and HCV envelope glycoproteins has been reported to take place during this process. SR-BI has been demonstrated to act during binding and postbinding steps of HCV entry. Although the SR-BI determinants involved in HCV binding have been partially characterized, the postbinding function of SR-BI remains largely unknown. To uncover the mechanistic role of SR-BI in viral initiation and dissemination, we generated a novel class of anti-SR-BI monoclonal antibodies that interfere with postbinding steps during the HCV entry process without interfering with HCV particle binding to the target cell surface. Using the novel class of antibodies and cell lines expressing murine and human SR-BI, we demonstrate that the postbinding function of SR-BI is of key impact for both initiation of HCV infection and viral dissemination. Interestingly, this postbinding function of SR-BI appears to be unrelated to HDL interaction but to be directly linked to its lipid transfer function. Conclusion: Taken together, our results uncover a crucial role of the SR-BI postbinding function for initiation and maintenance of viral HCV infection that does not require receptor-E2/HDL interactions. The dissection of the molecular mechanisms of SR-BI-mediated HCV entry opens a novel perspective for the design of entry inhibitors interfering specifically with the proviral function of SR-BI. (HEPATOLOGY 2013;57:492-504) H epatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Preventive modalities are nonexistent, and the current antiviral treatment is limited by resistance, toxicity, and high cost. 1 Viral entry is required for initiation, spread, and maintenance of infection, and thus is a promising target for antiviral therapy. HCV binding and entry into hepatocytes is a complex process involving the viral envelope glycoproteins E1 and E2, as well as several host factors,

LBA3 Background: Cervical cancer is a common cause of cancer-related death among women worldwide. Standard treatment for locally advanced disease is chemoradiation. However, a significant percentage of women still relapse and die from the development of distant metastatic disease. OUTBACK was designed to determine the effects of giving adjuvant chemotherapy after chemoradiation on survival. Methods: OUTBACK is an international randomized phase III trial of the Gynecologic Cancer InterGroup (GCIG). Participating groups (countries) included ANZGOG (Australia and New Zealand), NRG (USA, Saudi Arabia, Canada, China), and Singapore. Eligible women had locally advanced cervical cancer (FIGO 2008 stage IB1 and node positive, IB2, II, IIIB or IVA) that was suitable for primary treatment with chemo-radiation with curative intent. Women were randomly assigned to either standard cisplatin-based chemo-radiation (control) or standard cisplatin-based chemo-radiation followed by adjuvant chemotherapy (ACT) with 4 cycles of carboplatin and paclitaxel, after stratification for nodal status, participating site, FIGO stage, age, and planned extended-field radiotherapy. The primary end point was overall survival (OS) at 5 years. Secondary endpoints included progression-free survival (PFS); adverse events (AE); and patterns of disease recurrence. The target sample size of 900 provided 80% power with 95% confidence to detect an improvement in OS at 5 years from 72% (control) to 80% (ACT), with some over-accrual to account for non-compliance with ACT and loss to follow-up. Results: 919 of 926 women recruited from April 2011 to June 2017 were eligible and included in the primary analysis: 463 assigned ACT, 456 control. ACT was started in 361 (78%) women assigned to receive it. Median follow-up was 60 months (IQR 45-65). OS at 5 years was similar in those assigned ACT versus control (72% vs 71%, difference <1%, 95% CI -6 to +7; P = 0.91). The hazard ratio for OS was 0·91, (95% CI 0.70 to 1.18). PFS at 5 years was similar in those assigned ACT versus control (63% vs 61%, difference 2%, 95% CI -5 to +9; P = 0.61). The hazard ratio for PFS was 0·87, (95% CI 0.70 to 1.08). AE of grade 3-5 within a year of randomisation occurred in 81% who were assigned and received ACT versus 62% assigned control. There was no evidence of differences between treatment groups in AE beyond 1 year of randomisation. Patterns of disease recurrence were similar in the two treatment groups. Conclusions: Adjuvant chemotherapy given after standard cisplatin-based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS. Clinical trial information: ACTRN12610000732088.