Increased CD112 expression in methylcholanthrene-induced tumors in CD155-deficient mice.
Tumor recognition by immune effector cells is mediated by antigen receptors and a variety of adhesion and costimulatory molecules. The evidence accumulated since the identification of CD155 and CD112 as ligands for DNAM-1 in humans and mice has suggested that the interactions between DNAM-1 and its ligands play an important role in T cell- and natural killer (NK) cell-mediated recognition and lysis of tumor cells. We have previously demonstrated that methylcholanthrane (MCA) accelerates tumor development in DNAM-1-deficient mice, and the Cd155 level on MCA-induced tumors is significantly higher in DNAM-1-deficient mice than in wild-type (WT) mice. By contrast, Cd112 expression on the tumors is similar in WT and DNAM-1-deficient mice, suggesting that CD155 plays a major role as a DNAM-1 ligand in activation of T cells and NK cells for tumor immune surveillance. To address this hypothesis, we examined MCA-induced tumor development in CD155-deficient mice. Unexpectedly, we observed no significant difference in tumor development between WT and CD155-deficient mice. Instead, we found that Cd112 expression was significantly higher in the MCA-induced tumors of CD155-deficient mice than in those of WT mice. We also observed higher expression of DNAM-1 and lower expression of an inhibitory receptor, TIGIT, on CD8+ T cells in CD155-deficient mice. These results suggest that modulation of the expression of receptors and CD112 compensates for CD155 deficiency in immune surveillance against MCA-induced tumors.
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan; Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Yoko
Y
Nagumo
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Department of Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Akiko
A
Iguchi-Manaka
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Japan.
Yumi
Y
Yamashita-Kanemaru
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Japan.
Fumie
F
Abe
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Günter
G
Bernhardt
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Japan; Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan.
Akira
A
Shibuya
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Kazuko
K
Shibuya
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005354:Fibrosarcoma / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000075983:Nectins; D009363:Neoplasm Proteins / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000098862:T Lineage-Specific Activation Antigen 1; D015815:Cell Adhesion Molecules; D016207:Cytokines; D053646:Interleukin-2 Receptor beta Subunit; D000075983:Nectins; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; C556305:T cell Ig and ITIM domain protein, mouse; C476587:Taa1 protein, mouse; D008748:Methylcholanthrene