Increased CD112 expression in methylcholanthrene-induced tumors in CD155-deficient mice

PLoS One. 2014 Nov 10;9(11):e112415. doi: 10.1371/journal.pone.0112415. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Neoplasm / genetics*
  • Cell Adhesion Molecules / genetics*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Fibrosarcoma / chemically induced*
  • Fibrosarcoma / genetics
  • Fibrosarcoma / pathology*
  • Humans
  • Interleukin-2 Receptor beta Subunit / genetics
  • Killer Cells, Natural / metabolism
  • Male
  • Methylcholanthrene / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nectins
  • Neoplasm Proteins / genetics*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • CD226 antigen
  • Cell Adhesion Molecules
  • Cytokines
  • Interleukin-2 Receptor beta Subunit
  • Nectins
  • Neoplasm Proteins
  • Receptors, Immunologic
  • T cell Ig and ITIM domain protein, mouse
  • Taa1 protein, mouse
  • Methylcholanthrene

Grants and funding

This research was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant Number 24249021 and 25114701 to AS and KS, respectively). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.