title: Activation of a helper and not regulatory human CD4+ T cell response by oncolytic H-1 parvovirus.
abstract: BACKGROUND
  H-1 parvovirus (H-1 PV), a rodent autonomous oncolytic parvovirus, has emerged as a novel class of promising anticancer agents, because of its ability to selectively find and destroy malignant cells. However, to probe H-1 PV multimodal antitumor potential one of the major prerequisites is to decipher H-1 PV direct interplay with human immune system, and so prevent any risk of impairment.
  
  
  RESULTS
  Non activated peripheral blood mononuclear cells (PBMCs) are not sensitive to H-1 PV cytotoxic effect. However, the virus impairs both activated PBMC proliferation ability and viability. This effect is related to H-1 PV infection as evidenced by Western blotting detection of H-1 PV main protein NS1. However, TCID50 experiments did not allow newly generated virions to be detected. Moreover, flow cytometry has shown that H-1 PV preferentially targets B lymphocytes. Despite seeming harmful at first sight, H-1 PV seems to affect very few NK cells and CD8+ T lymphocytes and, above all, clearly does not affect human neutrophils and one of the major CD4+ T lymphocyte subpopulation. Very interestingly, flow cytometry analysis and ELISA assays proved that it even activates human CD4+ T cells by increasing activation marker expression (CD69 and CD30) and both effective Th1 and Th2 cytokine secretion (IL-2, IFN-γ and IL-4). In addition, H-1 PV action does not come with any sign of immunosuppressive side effect. Finally, we have shown the efficiency of H-1 PV on xenotransplanted human nasopharyngeal carcinoma, in a SCID mouse model reconstituted with human PBMC.
  
  
  CONCLUSIONS
  Our results show for the first time that a wild-type oncolytic virus impairs some immune cell subpopulations while directly activating a Helper CD4+ T cell response. Thus, our data open numerous gripping perspectives of investigation and strongly argue for the use of H-1 PV as an anticancer treatment.
authors.affiliation: Institut de Biologie de Lille, UMR 8161, CNRS, Institut Pasteur de Lille, Université Lille-Nord de France, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Moralès
authors.forename: Audrey
authors.initials: A
authors.lastname: Richard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Martin
authors.forename: Dhafer
authors.initials: D
authors.lastname: Mrizak
authors.forename: Magalie
authors.initials: M
authors.lastname: Sénéchal
authors.forename: Céline
authors.initials: C
authors.lastname: Miroux
authors.forename: Véronique
authors.initials: V
authors.lastname: Pancré
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Perrine
authors.initials: P
authors.lastname: Caillet-Fauquet
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.forename: Nadira
authors.initials: N
authors.lastname: Delhem
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002277:Carcinoma; D052661:H-1 parvovirus / Q000276:immunology*; D006801:Humans; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy; D050504:Oncolytic Viruses / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory; D023041:Xenograft Model Antitumor Assays