Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

<p>Abstract</p> <p>Background</p> <p>Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.</p> <p>Methods</p> <p>We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for <it>HLA-DQA1</it>, <it>DRB1 </it>and <it>DQB1 </it>genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.</p> <p>Results</p> <p>European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between <it>DQB1*05 </it>(adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of <it>HLA DRB1*1302 </it>carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with <it>DRB1*15 </it>was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between <it>DRB1*04 </it>and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the <it>E6 </it>gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between <it>DQB1*05 </it>and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89).</p> <p>Conclusion</p> <p>Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.</p

A Novel Therapy for Melanoma Developed in Mice: Transformation of Melanoma into Dendritic Cells with Listeria monocytogenes

Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used in cancer immunotherapy because of its capacity to induce a specific cytotoxic T cell response in tumours. This bacterial pathogen strongly induces innate and specific immunity with the potential to overcome tumour induced tolerance and weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma based in its tropism for these tumour cells and its ability to transform in vitro and in vivo melanoma cells into matured and activated dendritic cells with competent microbicidal and antigen processing abilities. This Listeria based vaccination using low doses of the pathogen caused melanoma regression by apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent and implies the reduction of LLO-specific CD4+ T cell responses, strong stimulation of innate pro-inflammatory immune cells and a prevalence of LLO-specific CD8+ T cells involved in tumour regression and Listeria elimination. These results support the use of low doses of pathogenic Listeria as safe melanoma therapeutic vaccines that do not require antibiotics for bacterial removal