Anti-HPV16 E2 Protein T-Cell Responses and Viral Control in Women with Usual Vulvar Intraepithelial Neoplasia and Their Healthy Partners

T-cell responses (proliferation, intracellular cytokine synthesis and IFNγ ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during 18 months in a longitudinal study in eight women presenting with HPV16-related usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In six women, anti-E2 proliferative responses and cytokine production (single IFNγ and/or dual IFNγ/IL2 and/or single IL2) by CD4+ T lymphocytes became detectable after treating and healing of the usual VIN. In the women presenting with persistent lesions despite therapy, no proliferation was observed. Anti-E2 proliferative responses were also observed with dual IFNγ/IL2 production by CD4+ T-cells in six male partners who did not exhibit any genital HPV-related diseases. Ex vivo IFNγ ELISPOT showed numerous effector T-cells producing IFNγ after stimulation by a dominant E2 peptide in all men and women. Since the E2 protein is absent from the viral particles but is required for viral DNA replication, these results suggest a recent infection with replicative HPV16 in male partners. The presence of polyfunctional anti-E2 T-cell responses in the blood of asymptomatic men unambiguously establishes HPV infection even without detectable lesions. These results, despite the small size of the studied group, provide an argument in favor of prophylactic HPV vaccination of young men in order to prevent HPV16 infection and viral transmission from men to women

Hormone induced maturation of Xenopus laevis oocytes: Effects of different steroids and study of the properties of a progesterone receptor

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Unique Functional Status of Natural Killer Cells in Metastatic Stage IV Melanoma Patients and Its Modulation by Chemotherapy

International audiencePurpose: Immunotherapy is an alternative for metastatic melanoma patients resistant to chemotherapy. Natural killer (NK) cells are powerful antileukemia effectors and their role in solid tumors is suspected. NK cell activation is regulated by a balance between activating receptors, which detect stress molecules on tumor cells, and HLA-I specific inhibitory receptors. Here, we studied the phenotype and function of NK cells in stage IV metastatic melanoma patients. Experimental Design: Circulating NK cells from 35 healthy donors and 51 patients were studied: 24 patients before chemotherapy (prechemotherapy), 17 patients 1 month after 1 to 4 lines of chemotherapy (postchemotherapy), and 10 patients analyzed pre-and postchemotherapy. NK functionality was carried out toward 2 primary metastatic melanoma cell lines, analyzed for the expression of NK receptor ligands. Results: NK cells from prechemotherapy patients exhibit an NKp46 dim /NKG2A dim phenotype. In contrast, NK cells from postchemotherapy patients display high expression of NKp46 and NKG2A receptors. Purified NK cells from patients are efficiently activated in response to melanoma cells. Melanoma cells express different level of NKG2D ligands and HLA-I molecules. In agreements with their phenotype, NK cells from pre-and postchemotherapy patients present distinct functional status toward these primary melanoma cells. A dynamic label free assay was used to determine the pathways involved in the lysis of melanoma cells by IL-2-activated NK cells. NKG2D, NCR (natural cytotoxicity receptor), and DNAM-1 are involved in the NK-mediated lysis of melanoma cells. Conclusions: These results provide new arguments and clues to design NK cell-based immunotherapeutic strategies for melanoma patients. Clin Cancer Res; 17(9); 2628-37. Ó2011 AACR