CD8(+) T-cell immunity against cancer-testis antigens develops following allogeneic stem cell transplantation and reveals a potential mechanism for the graft-versus-leukemia effect.
BACKGROUND
Allogeneic stem cell transplantation is associated with a powerful 'graft-versus-leukemia' effect that is generally considered to result from an alloreactive T-cell immune response. However, disease remission can also be observed after syngeneic transplantation and we investigated whether a T-cell immune response to cancer-testis antigens can be detected in patients in the post-transplant period.


METHODS
The T-cell immune response against cancer-testis antigens was studied in a cohort of 41 patients who underwent allogeneic stem cell transplantation for the management of acute myeloid leukemia or multiple myeloma. The cytokine secretion assay was combined with magnetic selection to allow detection of an interferon-gamma-secreting T-cell response to a panel of cancer-testis antigen peptides.


RESULTS
A cancer-testis antigen-specific CD8(+) T-cell immune response was observed in the peripheral blood of five patients with an average magnitude of 0.045% of the CD8(+) T-cell repertoire. Four of these patients had undergone reduced intensity conditioning transplantation with alemtuzumab for the treatment of acute myeloid leukemia and three remain in long-term remission. T-cell immunity was focused against peptides derived from MAGE proteins and was markedly increased within the bone marrow.


CONCLUSIONS
Functional cancer-testis antigen-specific CD8(+) T-cell immune responses develop in the early period following reduced intensity allogeneic stem cell transplantation and are preferentially localized to bone marrow. These immune responses are likely to contribute to the cellular basis of the graft-versus-leukemia effect.
McLarnon
Andrew
A
School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT UK.
Piper
Karen P
KP
Goodyear
Oliver C
OC
Arrazi
Julie M
JM
Mahendra
Premini
P
Cook
Mark
M
Clark
Fiona
F
Pratt
Guy
G
Craddock
Charles
C
Moss
Paul A H
PA
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007111:Immunity, Cellular; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D013737:Testis / Q000276:immunology; D055815:Young Adult
D000951:Antigens, Neoplasm
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