NKG2D defines tumor-reacting effector CD8+ T cells within tumor microenvironment

Cancer Sci. 2021 Sep;112(9):3484-3490. doi: 10.1111/cas.15050. Epub 2021 Jul 28.

Abstract

For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8+ T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8+ T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8+ cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8+ T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8+ T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8+ T cells.

Keywords: NKG2D; TOX; cytotoxic T cell; immune surveillance; tumor microenvironment.

MeSH terms

  • Animals
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / metabolism
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Bromodeoxyuridine / administration & dosage
  • Bromodeoxyuridine / pharmacokinetics
  • CD8-Positive T-Lymphocytes / immunology*
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Luciferases / metabolism
  • Luminescent Measurements / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Ovalbumin / administration & dosage
  • Ovalbumin / metabolism
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Tumor Microenvironment / immunology*
  • Vaccination / methods

Substances

  • Antigens, Neoplasm
  • Antimetabolites, Antineoplastic
  • IFNG protein, mouse
  • Klrk1 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily K
  • Interferon-gamma
  • Ovalbumin
  • Luciferases
  • Bromodeoxyuridine