Increased CD112 Expression in Methylcholanthrene-Induced Tumors in CD155-Deficient Mice

• Published in: PLoS ONE Vol. 9; no. 11; p. e112415
• Main Authors: 南雲 陽子, 渋谷 彰, 渋谷 和子, Nagumo Yoko, Iguchi-Manaka Akiko, Abe Fumie, Bernhardt Günter, Shibuya Akira, Shibuya Kazuko
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.11.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Neoplasm - genetics; Biology and Life Sciences; Cancer; CD226 antigen; CD8 antigen; Cell activation; Cell Adhesion Molecules - genetics; Costimulator; Cytokines; Cytokines - genetics; Cytokines - metabolism; Cytotoxicity; Dendritic cells; Effector cells; Fibrosarcoma; Fibrosarcoma - chemically induced; Fibrosarcoma - genetics; Fibrosarcoma - pathology; Flow cytometry; Humans; Immunology; Immunosurveillance; Interleukin-2 Receptor beta Subunit - genetics; Killer Cells, Natural - metabolism; Ligands; Lymphocytes; Lymphocytes T; Lysis; Male; Medical research; Medicine; Methylcholanthrene - toxicity; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Natural killer cells; Nectins; Neoplasm Proteins - genetics; Receptors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Recognition; Rodents; Science; Surveillance; T cells; T-Lymphocytes - metabolism; Transcription factors; Tumor cells; Tumors; Japan; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112415

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.