Immunosurveillance of childhood ALL – Polymorphic Interferon-γ alleles are associated with age at diagnosis and clinical risk groups

In order to answer the question whether a defined CA-repeat in the IFNγ-gene -associated with IFNγ-expression levels- may influence the incidence, manifestation and early clinical treatment response of childhood ALL, we performed PCR-based genotyping of 393 patients with ALL (302 B-lineage, 69 T-lineage, 22 non classified) and 207 healthy controls. We could not find any difference in the allele distribution of ALL patients and controls. However, with respect to age of clinical manifestation, patients with B-lineage ALL showing the IFNγ high-expressing genotype presented at a more advanced age compared to those patients with intermediate and low expressing genotypes (median 6 versus 4.3 and 4.7 years, p=0.01). We also attempted to correlate the CA-repeat with clinical risk parameters defined by the ALL-BFM2000 study. In patients with B-lineage ALL, we found a significantly higher number of low expressors in the group of high-risk patients (HR n=32 and MR/SR n=266, p=0.025) and prednisone poor responders (poor responder n=17, good responder n=266, p=0.008). Our results suggest that IFNγ mediates antitumor immunity and thus support the concept of IFNγ dependent tumor surveillance in humans.