Human T cells interacting with HNSCC-derived mesenchymal stromal cells acquire tissue-resident memory like properties

Eur J Immunol. 2020 Oct;50(10):1571-1579. doi: 10.1002/eji.202048544. Epub 2020 Jun 2.

Abstract

Tissue-resident memory (Trm) cells are specialized components of both CD4+ and CD8+ T cell subsets that persist in peripheral nonlymphoid tissues following infections and provide fast response in case of a secondary invasion by the same pathogen. Trm cells express the surface markers CD69, CD103, and the immune checkpoint molecule PD-1. Trm cells develop not only in the context of infections but also in tumors, where they can provide a line of defense as suggested by the positive correlation between the frequency of tumor-infiltrating Trm cells and patients' survival. Trm cells persistence in peripheral tissues depends on their adaptation to the local microenvironment and the presence of survival factors, mainly IL-7, IL-15, and Notch ligands. However, the cell sources of these factors are largely unknown, especially in the context of tumors. Here, we show that head-neck squamous cell carcinoma (HNSCC) is enriched in CD4+ and CD8+ T cells with a Trm phenotype. Moreover, we show that mesenchymal stromal cells that accumulate in HNSCC are a source of survival factors and allow proper expression of Trm-typical markers in a VCAM1-dependent manner.

Keywords: HNSCC; Stromal cells; T cells; Tissue-resident memory; VCAM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Squamous Cell / immunology*
  • Cell Communication
  • Cell Movement
  • Cells, Cultured
  • Head and Neck Neoplasms / immunology*
  • Humans
  • Immunologic Memory
  • Interleukin-15 / metabolism
  • Interleukin-7 / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mesenchymal Stem Cells / immunology*
  • Phenotype
  • Receptors, Notch / metabolism
  • Tumor Microenvironment
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Interleukin-15
  • Interleukin-7
  • Receptors, Notch
  • Vascular Cell Adhesion Molecule-1