title: Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK.
abstract: Polysaccharide K (PSK) is a widely used mushroom extract that has shown anti-tumor and immunomodulatory effects in both preclinical and clinical studies. Therefore, it is important to understand the mechanism of actions of PSK. We recently reported that PSK can activate toll-like receptor 2 and enhances the function of NK cells. The current study was undertaken to study the effect of PSK on gamma delta (γδ) T cells, another important arm of the innate immunity. In vitro experiments using mouse splenocytes showed that γδ T cells produce IFN-γ after treatment with PSK and have up-regulated expression of CD25, CD69, and CD107a. To investigate whether the effect of PSK on γδ T cells is direct or indirect, purified γδ T cells were cultured either alone or together with bone marrow-derived DC in a co-culture or trans-well system and then stimulated with PSK. Results showed that direct cell-to-cell contact between γδ T cells and DC is required for optimal activation of γδ T cells. There was also reciprocal activation of DC by PSK-activated γδ T cells, as demonstrated by higher expression of costimulatory molecules and enhanced production of IL-12 by DC in the presence of γδ T cells. PSK can also co-stimulate γδ T cells with anti-TCR and anti-CD3 stimulation, in the absence of DC. Finally, in vivo treatment with PSK activates γδ T cells among the tumor infiltrating lymphocytes, and depleting γδ T cells during PSK treatment attenuated the anti-tumor effect of PSK. All together, these results demonstrated that γδ T cells are activated by PSK and contribute to the anti-tumor effect of PSK.
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Inatsuka
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ekram
authors.initials: E
authors.lastname: Gad
authors.forename: Lauren
authors.initials: L
authors.lastname: Rastetter
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011509:Proteoglycans / Q000276:immunology* / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017252:CD3 Complex; D052118:Lysosomal-Associated Membrane Protein 1; D011509:Proteoglycans; D016692:Receptors, Antigen, T-Cell, gamma-delta; C010770:polysaccharide-K; D007371:Interferon-gamma