Preferential Homing of Tumor-specific and Functional CD8+ Stem Cell-like Memory T Cells to the Bone Marrow

J Immunother. 2019 Jul/Aug;42(6):197-207. doi: 10.1097/CJI.0000000000000273.

Abstract

The bone marrow (BM) harbors not only hematopoietic stem cells but also conventional memory T and B cells. Studies of BM-resident memory T cells have revealed the complex relationship between BM and immunologic memory. In the present study, we identified CD122 stem cells antigen-1 (Sca-1), B-cell lymphoma protein-2 (Bcl-2), CD8 stem cell-like memory T cells (TSCMs) as a distinct memory T-cell subset preferentially residing in the BM, where these cells respond vigorously to blood-borne antigens. We found that the most TSCMs favorably relocate to the BM by adhesion molecules such as vascular cell adhesion protein 1, P-selectin glycoprotein 1, and P-selectin or E-selectin. Moreover, the BM-resident TSCMs exhibited much higher levels of antitumor activity than the spleen-resident TSCMs. These results indicate that the BM provides an appropriate microenvironment for the survival of CD8 TSCMs, thereby broadening our knowledge of the memory maintenance of antigen-specific CD8 T lymphocytes. The present findings are expected to be instructive for the development of tumor immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Bone Marrow / immunology*
  • Bone Marrow / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Movement / immunology
  • Immunologic Memory*
  • Immunotherapy
  • Melanoma, Experimental
  • Membrane Glycoproteins / metabolism
  • Mice
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Tumor Microenvironment / immunology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Biomarkers
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Vascular Cell Adhesion Molecule-1