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

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 CD122high stem cells antigen-1 (Sca-1)high, B-cell lymphoma protein-2 (Bcl-2)high, 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.