Abstract:
:Some patients lose chimerism following nonmyeloablative hematopoietic cell transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We hypothesized that host-versus-graft (HVG) alloresponses might induce antitumor effects against recipient tumors. We explored this question in mice by administering recipient leukocyte infusions (RLIs) to mixed chimeras established with nonmyeloablative conditioning. Mixed chimeras were prepared in the B10.A (H2a)-->B6 (H2b) strain combination using depleting anti-T-cell monoclonal antibodies (mAbs), cyclophosphamide, and thymic irradiation. B6 myeloid leukemia cells (MMB3.19) were administered 7 days following donor lymphocyte infusion (DLI) or RLI on day 35. Conversion to full donor chimerism occurred without graft-versus-host disease (GVHD) following DLI, whereas RLI led to loss of chimerism. Both RLI and DLI significantly delayed tumor mortality. In another strain combination (B10.BR [H2k]-->BALB/c [H2d]), RLI-induced or spontaneous loss of chimerism was associated with antitumor effects against the host-type B-cell lymphoma A20. HCT was essential for the antitumor effect of RLI. RLI induced elevated serum interferon-gamma (IFN-gamma) levels, and recipient-derived IFN-gamma was critical for their antitumor effects. Thus, HVG reactions (spontaneous or induced by RLI) mediate antitumor effects against hematologic malignancies via a recipient-derived IFN-gamma-mediated mechanism. A novel approach to achieving anti-tumor effects without the risk of GVHD is suggested.
journal_name
Bloodjournal_title
Bloodauthors
Rubio MT,Kim YM,Sachs T,Mapara M,Zhao G,Sykes Mdoi
10.1182/blood-2002-12-3949subject
Has Abstractpub_date
2003-09-15 00:00:00pages
2300-7issue
6eissn
0006-4971issn
1528-0020pii
2002-12-3949journal_volume
102pub_type
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