Lymphocyte Transformation in Children With Neuroblastoma 1 2

Abstract

Using a simple fingerstick-whole blood technique, we demonstrated that patients with disseminated neuroblastoma have diminished lymphocyte responses to phytohemagglutinin (PHA) and that their sensitivity to antilymphocyte serum inhibition of PHA responses was increased over that of tumor-free controls. These altered immunologic reactivities led us to question the chronologic sequence between the occurrence of the tumor and the lymphocyte defect. Tumor-bearing patients had serum substances that exerted an inhibitory effect on the transformation responses of lymphocytes from unrelated normal individuals; these substances may be present in sera for long periods after the tumor is eliminated.

Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

“…When subsequently looking into the functionality of T-cells at diagnosis and during the therapy regimen, we noticed hampered proliferation and cytokine secretion upon anti-CD3-mediated T-cell stimulation. In line with this, impaired PHA mitogenesis at diagnosis and during NBL therapy has been observed in several studies [ 30 , 31 ]. Helson et al [ 31 ] and Pelizzo et al [ 32 ] showed hampered PHA-mediated T-cell mitogenesis when cultures were supplemented with serum of NBL-patients, or mesenchymal stromal cells (MSCs) from HR-NBL patients, respectively.…”

“…In line with this, impaired PHA mitogenesis at diagnosis and during NBL therapy has been observed in several studies [ 30 , 31 ]. Helson et al [ 31 ] and Pelizzo et al [ 32 ] showed hampered PHA-mediated T-cell mitogenesis when cultures were supplemented with serum of NBL-patients, or mesenchymal stromal cells (MSCs) from HR-NBL patients, respectively. This indicates the presence of both local and systemic immune modulation by the NBL tumor.…”

Immune evaluation of 50 children with neuroblastoma at onset

“…cases of these last three this decrease was associated with normal values of T and B cells, thus suggesting a deficit of "null" cell population. Reactivity to mitogens was severely affected in most patients, independently from their clinical stage; Helson, too, found an impairment of PHA-response[8], while Chung found normal values[9]. Serum Ig level abnormalities were more frequently seen in advanced cases; high IgM values represented the most common alteration.…”

“…According to Bill and Morgan [4], a low number of lymphocytes at diagnosis would represent an unfavourable factor, but only when patients are under one year of age. Helson et a1 have shown an impairment of cell-mediated immune response both in vivo-by testing DNCB sensitivity [7] and in vitroby assessing lymphocyte transformation by phytohemagglutinin (PHA) [8]. Cellular responsiveness was diminished in parallel with disease extent.…”