title: Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role.
abstract: Tumor cells can induce certain cytokines and soluble receptors that have a suppressive effect on the immune system. In this study, we showed that an extracellular portion of a membrane-bound ligand of CD40 (soluble CD40 ligand; sCD40L) was significantly elevated in the serum of cancer patients compared with healthy donors. In addition, PBMCs from cancer patients had a relatively larger population of myeloid-derived suppressor cells (MDSCs), defined as CD33(+)HLA-DR(-) cells, and these cells expressed higher levels of CD40. T-cell proliferation and IFN-γ production decreased when stimulated T cells were cocultured with an increased amount of autologous MDSCs. The addition of recombinant monomeric sCD40L enriched MDSCs and had an additive inhibitory effect on T-cell proliferation. PBMCs cultured in vitro with sCD40L also showed an expansion of regulatory T cells (CD4(+)CD25(high)Foxp3(+)), as well as induction of cytokines, such as IL-10 and IL-6. Moreover, sCD40L-induced enrichment of programmed death-1-expressing T cells was greater in cancer patients than in healthy donors. Preexisting sCD40L also inhibited IL-12 production from monocytes on activation. These data suggest that the higher levels of sCD40L seen in cancer patients may have an immunosuppressive effect.
authors.affiliation: Laboratory of Tumor Immunology and Biology, 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: Tara
authors.initials: T
authors.lastname: Talaie
authors.forename: Austin
authors.initials: A
authors.lastname: Anderson
authors.forename: Alessandra
authors.initials: A
authors.lastname: Jales
authors.forename: Kwong Y
authors.initials: KY
authors.lastname: Tsang
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
mesh_terms: D000328:Adult; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D017322:Clinical Trials, Phase II as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009369:Neoplasms / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10; D023201:CD40 Ligand