NK cells infiltrating a MHC class I-deficient lung adenocarcinoma display impaired cytotoxic activity toward autologous tumor cells associated with altered NK cell-triggering receptors

J Immunol. 2005 Nov 1;175(9):5790-8. doi: 10.4049/jimmunol.175.9.5790.

Abstract

NK cells are able to discriminate between normal cells and cells that have lost MHC class I (MHC-I) molecule expression as a result of tumor transformation. This function is the outcome of the capacity of inhibitory NK receptors to block cytotoxicity upon interaction with their MHC-I ligands expressed on target cells. To investigate the role of human NK cells and their various receptors in the control of MHC-I-deficient tumors, we have isolated several NK cell clones from lymphocytes infiltrating an adenocarcinoma lacking beta2-microglobulin expression. Unexpectedly, although these clones expressed NKG2D and mediated a strong cytolytic activity toward K562, Daudi and allogeneic MHC-class I+ carcinoma cells, they were unable to lyse the autologous MHC-I- tumor cell line. This defect was associated with alterations in the expression of natural cytotoxicity receptor (NCR) by NK cells and the NKG2D ligands, MHC-I-related chain A, MHC-I-related chain B, and UL16 binding protein 1, and the ICAM-1 by tumor cells. In contrast, the carcinoma cell line was partially sensitive to allogeneic healthy donor NK cells expressing high levels of NCR. Indeed, this lysis was inhibited by anti-NCR and anti-NKG2D mAbs, suggesting that both receptors are required for the induced killing. The present study indicates that the MHC-I-deficient lung adenocarcinoma had developed mechanisms of escape from the innate immune response based on down-regulation of NCR and ligands required for target cell recognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic*
  • Histocompatibility Antigens Class I / physiology*
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis
  • Killer Cells, Natural / immunology*
  • Lung Neoplasms / immunology*
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / physiology*
  • Receptors, Natural Killer Cell
  • Tumor Escape

Substances

  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • Lymphocyte Function-Associated Antigen-1
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Intercellular Adhesion Molecule-1