title: Dendritic cells primed with HPV positive cervical tumor lysate are superior to unprimed DCs in migratory capacity and induce a potent Th1 response.
abstract: In this study, we assessed the efficacy of tumor lysate primed and unprimed monocyte derived mature dendritic cells (DCs) to trigger an effective anti-tumor immune response in cervical cancer patients who tested positive for human papilloma virus (HPV) DNA. Lysate primed and unprimed DCs were assessed for the expression of CD80, CD86, CD40, HLADR and CD83. The ability of DCs to migrate in response to the chemokines CCL19 and 21 as well as their ability to secrete IL12p40 was investigated. Mixed lymphocyte proliferation assays were used to assess DC stimulatory capacity and their ability to generate a Th1 response. Our results showed no difference in phenotypic expression between primed and unprimed DCs but both had significantly increased expression of the activation marker CD83 when compared to immature DCs. Importantly, the primed DCs showed significant (P value=0.03) IL-12p40 secretion and a superior migratory capacity towards CC19 and CCL21 (P value=0.04) compared to unprimed DCs even after cytokine withdrawal. Primed DCs showed superior stimulation of T cell proliferation (allogeneic and autologous) and secretion of IFN gamma (IFN-γ) than the unprimed DCs. Hence whole tumor lysate primed mature DCs could be potent immunotherapeutic adjuvants to standard treatment for cervical cancer.
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), India.
authors.forename: Priya
authors.initials: P
authors.lastname: Ramanathan
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), India.
authors.forename: Hemavathi
authors.initials: H
authors.lastname: Dhandapani
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), India.
authors.forename: Hascitha
authors.initials: H
authors.lastname: Jayakumar
authors.affiliation: Department of Radiation Oncology, Cancer Institute (WIA), India.
authors.forename: Selvaluxmy
authors.initials: S
authors.lastname: Ganeshrajah
authors.affiliation: Department of Molecular Oncology, Cancer Institute (WIA), India. Electronic address: drtrajkumar@gmail.com.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Thangarajan
mesh_terms: D000276:Adjuvants, Immunologic; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D054415:Chemokine CCL19 / Q000494:pharmacology; D054421:Chemokine CCL21 / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology; D027383:Papillomaviridae; D018417:Th1 Cells / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*; D000097802:CD83 Antigen
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D004279:DNA, Viral; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C497964:CD86 protein, human
keywords: Cervical cancer; Dendritic cells; HPV; IL-12p40; Th1 response