Bone marrow contains melanoma-reactive CD8+ effector T cells and, compared with peripheral blood, enriched numbers of melanoma-reactive CD8+ memory T cells.
Circulating melanoma-specific T cells can be frequently detected in patients with melanoma. Effective T-cell immunity and tumor surveillance, however, requires the presence of specific T cells in tissues populated by tumor cells. The bone marrow (BM) is a compartment frequently harboring micrometastatic tumor cells. Here, we compared directly ex vivo in peripheral blood (PB) and BM frequencies and differentiation phenotypes of T cells reactive with the melanoma-associated antigen tyrosinase and with autologous melanoma cells. Using intracellular cytokine and tetramer staining, we detected tyrosinase- and melanoma-reactive CD3+CD8+ T cells in the BM in similar or enhanced frequencies as in PB. Additional characterization of the differentiation subset using CD45RA and CCR7 revealed the presence of specific effector and memory T cells in the BM in all five patients analyzed. Remarkably, the frequency of tyrosinase- and melanoma-specific memory T cells was significantly increased in BM compared with PB. Thus, the BM may be an important compartment for tumor surveillance harboring a tumor-specific memory T-cell pool in addition to effector T cells.
D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005134:Eye Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D014442:Monophenol Monooxygenase / Q000097:blood / Q000276:immunology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000276:immunology; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism
D019718:Receptors, CXCR4; D014442:Monophenol Monooxygenase