title: Increased Soluble CD226 in Sera of Patients with Cutaneous T-Cell Lymphoma Mediates Cytotoxic Activity against Tumor Cells via CD155.
abstract: Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances. CD155 is expressed in various types of cancer, and this surface molecule on tumor cells functions either as a co-stimulatory molecule or a co-inhibitory molecule, depending on its receptor. CD226, a CD155 ligand, is mainly expressed on natural killer cells and CD8+T cells, playing important roles in natural killer cell-mediated cytotoxicity. In this study, we investigated the expression and function of CD155 and CD226 in cutaneous T-cell lymphoma (CTCL). CD155 was strongly expressed on tumor cells and CD155 mRNA expression levels were increased in CTCL lesional skin. CD226 expression on natural killer cells and CD8+cells in peripheral blood of CTCL patients was decreased. On the other hand, serum CD226 levels were significantly elevated in CTCL patients, strongly reflecting disease activity, suggesting that soluble CD226 in sera was generated by shedding of its membrane form. Recombinant CD226 itself showed cytotoxic activity against CD155-expressing CTCL cells in vitro. These data suggest that soluble CD226 elevated in sera of CTCL patients would be important for tumor immunity by interacting with CD155 on tumor cells.
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. Electronic address: sugayam-der@h.u-tokyo.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Suga
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyagaki
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Dermatology, University of Yamanashi, Kofu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inozume
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics*; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D012334:RNA, Neoplasm; D011991:Receptors, Virus; C066100:poliovirus receptor