CD8+ T-cell responses to tumor-associated antigens correlate with superior relapse-free survival after allo-SCT.
The GVL effect following allo-SCT is one of the most prominent examples showing the ability of the immune system to eliminate malignant hematological diseases. Tumor-associated Ags (TAA), for instance WT1 and proteinase-3, have been proposed as targets for T cells to establish a GVL effect. Here, we examined an additional TAA (MUC1) as a possible T-cell target of GVL-related immune responses. We have defined new peptide epitopes from the MUC1 Ag to broaden patients' screening and to expand the repertoire of immunologic monitoring as well as for therapeutic approaches in the future. Twenty-eight patients after allo-SCT have been screened for T-cell responses toward TAA (proteinase-3, WT1, MUC1). We could detect a significant relationship between relapse and the absence of a TAA-specific T-cell response, whereby only 2/13 (15%) patients with TAA-specific CTL relapsed, in contrast to 9/15 (60%) patients without TAA-specific CTL responses (P<0.05). In conclusion, CD8(+) T-cell responses directed to TAA might contribute to the GVL effect. These observations highlight both the importance and the potential of immunotherapeutic approaches after allo-SCT.
Kapp
M
M
Medizinische Klinik und Poliklinik II, Julius-Maximilians-Universität, Würzburg, Germany.
Stevanović
S
S
Fick
K
K
Tan
S M
SM
Loeffler
J
J
Opitz
A
A
Tonn
T
T
Stuhler
G
G
Einsele
H
H
Grigoleit
G U
GU
D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D000939:Epitopes; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D018396:Mucin-1 / Q000276:immunology; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy; D012008:Recurrence; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; C060192:MUC1 protein, human; D018396:Mucin-1