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

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(high) stem cells antigen-1 (Sca-1)(high), B-cell lymphoma protein-2 (Bcl-2)(high), CD8(+) stem cell-like memory T cells (T(SCM)s) 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 T(SCM)s 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 T(SCM)s exhibited much higher levels of antitumor activity than the spleen-resident T(SCM)s. These results indicate that the BM provides an appropriate microenvironment for the survival of CD8(+) T(SCM)s, 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.