Tumor-immune memory T cells from the bone marrow exert GvL without GvH reactivity in advanced metastasized cancer.
The bone marrow has been shown to represent a unique microenvironment where T cell immune responses against tumor associated antigens can be initiated and tumor-immune memory T cells are enriched. In the present study the graft versus leukemia (GvL) reactivity of bone marrow derived tumor-immune memory T cells was analyzed in an allogeneic minor histocompatibility different murine GvL tumor model with late stage disease. A single adoptive cell transfer of B10.D2 donor immune bone marrow cells (iBM) into sub-lethally irradiated late stage ESb-MP tumor-bearing DBA/2 mice led to a complete tumor remission and to significant life prolongation. Even though the frequency of bone marrow resident T cells is only around 2%, the GvL reactivity of iBM was superior to immune cells from the spleen (iSPL) or to those from the peritoneal cavity (iPEC) of the same immunized donors. iPEC exerted mostly unwanted graft versus host (GvH) reactivity, while iSPL exerted GvL and GvH reactivity. Bone marrow cells from naive donor mice or T cell depleted iBM cells were completely devoid of GvL reactivity. The low number of tumor-immune memory T cells thus conferred the GvL reactivity of iBM cells.
Schirrmacher
Volker
V
German Cancer Research Center, Division of Cellular Immunology, D-69120 Heidelberg, Germany. v.schirrmacher@dkfz-heidelberg.de
Beckhove
Philipp
P
Choi
Carmen
C
Griesbach
Andreas
A
Mahnke
Yolanda
Y
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006087:Graft vs Host Reaction; D007107:Immune System / Q000378:metabolism; D007156:Immunologic Memory; D007700:Kinetics; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors