Role of LLT1 and PCNA as Natural Killer Cell Immune Evasion Strategies of HCT 116 Cells

Anticancer Res. 2020 Dec;40(12):6613-6621. doi: 10.21873/anticanres.14686. Epub 2020 Dec 7.

Abstract

Background/aim: Cancer stem cells (CSCs) are a subpopulation of cells that retain self-renewal and pluripotency capabilities, are resistant to chemotherapy, and are thought to facilitate metastasis. Target cell expression of proliferating cell nuclear antigen (PCNA) or lectin-like transcript 1 (LLT1) inhibits natural killer (NK) cell functions. The purpose of this study was to characterize the expression of LLT1 or PCNA as NK cell evasion strategies of HCT 116, a colorectal cancer cell line.

Materials and methods: Protein expression was determined by flow cytometry and/or confocal microscopy. Stem-like cells were sorted and characterized, and NK cell effector functions measured by interferon-γ secretion and cytotoxicity assay.

Results: PCNA expressing cells are potential CSCs, blocking PCNA alters interferon-γ secretion, and blocking PCNA or LLT1 increases cytotoxicity.

Conclusion: PCNA is a potential biomarker of stem-like colon cancer cells. Based on the results of this study, PCNA and LLT1 should be further explored as in vivo immunotherapeutic targets for NK cell-mediated killing.

Keywords: Natural killer cells; cancer stem cells; colorectal cancer; immune evasion; immunotherapy.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • HCT116 Cells
  • Humans
  • Immune Evasion*
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type / metabolism*
  • Ligands
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Natural Killer Cell / metabolism

Substances

  • Biomarkers, Tumor
  • CLEC2D protein, human
  • Lectins, C-Type
  • Ligands
  • Proliferating Cell Nuclear Antigen
  • Receptors, Cell Surface
  • Receptors, Natural Killer Cell
  • Interferon-gamma