title: Soluble CD27-pool in humans may contribute to T cell activation and tumor immunity.
abstract: The interaction between CD27 and its ligand, CD70, has been implicated in regulating cellular immune responses to cancer. In this article, we report on the role of soluble CD27 (sCD27) in T cell activation and its elevation in the serum of cancer patients after immunotherapy. In vitro, sCD27 is preferentially derived from activated CD4(+) T cells. Adding sCD27 to stimulated PBMCs increases T cell activation and proliferation, and is associated with the immunologic synapse-related proteins myosin IIA, high mobility group box 1, and the TCR Vβ-chain. The pool of serum sCD27 is shown to be greater in healthy donors than in cancer patients. However, metastatic cancer patients treated with immunotherapy showed a significant increase in the serum sCD27-pool posttherapy (p < 0.0005); there was also an increased trend toward an association between enhanced sCD27-pool posttherapy and overall survival (p = 0.022). The identification of sCD27 as an immune modulator associated with enhanced human T cell activation in vitro and in vivo provides a rationale for developing new immunotherapeutic strategies aimed at enhancing sCD27 for treating cancer and potentially other diseases.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Huang
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.forename: Austin M
authors.initials: AM
authors.lastname: Anderson
authors.forename: Tara
authors.initials: T
authors.lastname: Talaie
authors.forename: Alessandra
authors.initials: A
authors.lastname: Jales
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.forename: Kwong Y
authors.initials: KY
authors.lastname: Tsang
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D002469:Cell Separation; D002986:Clinical Trials as Topic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7