CD8+ T cells reactive to survivin antigen in patients with multiple myeloma.
OBJECTIVE
Survivin is a member of the inhibitors of apoptosis family and is overexpressed in different types of malignancies. Cytotoxic T cells recognizing survivin epitopes can be elicited in vitro and by vaccination in patients with leukemia, breast cancer, and melanoma. We did this study to investigate whether survivin-specific CD8+ T cells occur in patients with multiple myeloma.


METHODS
An HLA-A2.1-binding survivin peptide was used to detect peptide-specific T cells by a quantitative real-time PCR to measure antigen-specific IFN-gamma mRNA expression in 23 patients with myeloma and 21 healthy volunteers. T cells producing IFN-gamma in response to survivin were further analyzed for expression of CD45RA and CCR7 to determine phenotypic characterization. Additional immunohistochemical analyses of survivin antigen expression in bone marrow specimens of patients was done.


RESULTS
T cells recognizing HLA-A2.1-binding survivin peptide were detected in 9 of 23 patients and in 1 of 21 healthy volunteers. Survivin-reactive T cells were identified as terminally differentiated effector T cells (CD8+, CD45RA+, and CCR7-). Positive survivin expression of myeloma cells in bone marrow specimens was shown in 7 of 11 patients.


CONCLUSIONS
We provide, for the first time, evidence of T cell reactivity against survivin antigen in patients with multiple myeloma. Our data suggest the immunogenicity of survivin antigen in multiple myeloma and that immunotherapeutic strategies using survivin as a target antigen might be an option for patients with this disease.
Grube
Matthias
M
Department of Hematology and Oncology, Institute of Pathology, University of Regensburg, Regensburg, Germany. matthias.grube@klinik.uni-regensburg.de
Moritz
Stephanie
S
Obermann
Ellen C
EC
Rezvani
Katayoun
K
Mackensen
Andreas
A
Andreesen
Reinhard
R
Holler
Ernst
E
D000368:Aged; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D000939:Epitopes; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D000077022:Survivin
C107489:BIRC5 protein, human; C515370:CCR7 protein, human; D000939:Epitopes; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D000077022:Survivin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens