Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk.
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) constitutes an ideal model disease to study tumor-specific immune responses. All the tumor cells express oncogenic ALK resulting from a chromosomal translocation involved in lymphomagenesis. Although antibodies and T-cell responses to ALK have previously been detected in ALK-positive ALCL patients, their prognostic significance is unknown. We investigated a large cohort of uniformly treated ALK-positive pediatric ALCL patients to ascertain whether the titers of preexisting ALK autoantibodies correlated with clinical and histologic characteristics, tumor dissemination, and patient outcome. ALK autoantibodies were analyzed in pretherapeutic serum samples from 95 patients enrolled into 2 therapy studies between 1996 and 2007. ALK autoantibodies were detected in 87/95 patients. The titers inversely correlated with stage and amount of circulating tumor cells. High antibody titers correlated with significantly lower cumulative incidence of relapses (CI-R): titers > or = 1/60 750, n = 29, CI-R 11% +/- 6%; titers 1/2025-< 1/60 750, n = 39, CI-R 31% +/- 8%; and titers 0-< or = 1/750, n = 27, CI-R of 63% +/- 10% (P < .001). Our results provide the first clinical evidence that a robust preexisting immune response to an oncoantigen resulting from an oncogenic chromosomal translocation inhibits lymphoma dissemination and decreases the risk of relapse.
Ait-Tahar
Kamel
K
University of Oxford, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK.
Damm-Welk
Christine
C
Burkhardt
Birgit
B
Zimmermann
Martin
M
Klapper
Wolfram
W
Reiter
Alfred
A
Pulford
Karen
K
Woessmann
Wilhelm
W
D000293:Adolescent; D000077548:Anaplastic Lymphoma Kinase; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D053208:Kaplan-Meier Estimate; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000276:immunology*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases; D012307:Risk Factors; D016896:Treatment Outcome
D001323:Autoantibodies; D001324:Autoantigens; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases