Humoral immune responses against the immature laminin receptor protein show prognostic significance in patients with chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. The role of an autologous tumor-specific immune control contributing to the variable length of survival in CLL is poorly understood. We investigated whether humoral immunity specific for the CLL-associated Ag oncofetal Ag/immature laminin receptor (OFA/iLR) has a prognostic value in CLL. Among sera of 67 untreated patients with CLL, 23 (34.3%) had detectable OFA/iLR Abs that were reactive for at least one specific OFA/iLR epitope. Patients with humoral responses compared with patients with nonreactive sera had a longer progression-free survival (p = 0.029). IgG subclass analyses showed a predominant IgG1 and IgG3 response. OFA/iLR Abs were capable of recognizing and selectively killing OFA/iLR-expressing CLL cells in complement-mediated and Ab-dependent cellular cytotoxicity assays. In the analysis of 11 CLL patients after allogeneic hematopoietic stem cell transplantation, 8 showed high values for OFA/iLR Abs that specifically recognized the extracellular domain of the protein, suggesting a potential role of anti-OFA/iLR-directed immune responses to the graft-vs-leukemia effect in CLL. Our data suggest that spontaneous tumor-specific humoral immune responses against OFA/iLR exist in a significant proportion of CLL patients and that superior progression-free survival in those patients could reflect autologous immune control.
Friedrichs
Birte
B
Department of Hematology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, Hamburg, Germany.
Siegel
Sandra
S
Kloess
Marita
M
Barsoum
Adel
A
Coggin
Joseph
J
Rohrer
James
J
Jakob
Ilja
I
Tiemann
Markus
M
Heidorn
Klaus
K
Schulte
Christoph
C
Kabelitz
Dieter
D
Steinmann
Jörg
J
Schmitz
Norbert
N
Zeis
Matthias
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017474:Receptors, Laminin / Q000276:immunology*; D012269:Ribosomal Proteins / Q000276:immunology*; D015996:Survival Rate; D014184:Transplantation, Homologous
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; C031192:oncofetal antigens