title: An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites.
abstract: Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone.
authors.affiliation: Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas, USA.
authors.forename: Xinping
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Rivera
authors.affiliation: Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000276:immunology* / Q000502:physiology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D047368:Tumor Burden / Q000276:immunology; D014709:Vero Cells
chemical_list: D018925:Chemokines; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D019707:Receptors, Chemokine