Immunosuppressive effect of acute-phase reactant proteins in vitro and its relevance to cancer

Abstract

Acute-phase reactant proteins reach abnormally high levels in patients with cancer, and correlate with the extent of disease. In this study, several acute-phase glycoproteins, and serum albumin as a control, were tested at different concentrations for their ability to modify the blastogenic response of lymphocytes from 30 normal donors to PHA and the chemotactic response of monocytes from 15 normal donors to casein. In high concentrations approximating those found in cancer patients, but not in normal concentrations, haptoglobin and fibrinogen inhibited both functions to different degrees. Orosomucoid inhibited only monocyte chemotaxis, while ceruloplasmin and alpha 1-antitrypsin affected neither function. Increasing concentrations of PHA did not overcome the blocking effect of haptoglobin and fibrinogen on blastogenesis, suggesting that PHA-protein interaction was not responsible for the effect observed. The three proteins that did not suppress blastogenesis individually did so strongly when combined. It is suggested that these glycoproteins, synthesized by the liver in response to an inflammatory stimulus, may act as 'non-specific blocking factors' protecting tumors against the host's immunological attack. This non-specific blocking activity of the acute-phase proteins may contribute to the 'immune escape' of the tumor.

Serum Protein Profiling to Identify High-Risk Neuroblastoma: Preclinical Relevance of Blood-Based Biomarkers

“…Nevertheless, as APPs may not be NB-specific signatures for advanced disease, it has been postulated that APPs may exert a tumor-mediated immune suppression. Reports have implicated APPs acting as non-specific blocking factors protecting tumors against the host's immunological attack [33][34][35]. This notion is indirectly supported by our results which show overexpression of serum APPs in an animal NB progression model and preliminary human NB samples.…”

Acute-Phase Proteins in Alzheimer’s Disease

“…It was reported that an increased level of CER together with that of aAT and AaG can exert an immunosuppressive effect [14], However, in our study, only CER was found to be elevated and therefore such a synergic immunosuppressive effect cannot be expected.…”

“…The aAT has an inhibiting effect on macrophages and inhibits lymphocyte proliferation to phytohemagglutinin (PHA) [12], The latter effect seems to be due to a decreased production of IL-1 by macrophages [13]. A synergic effect of these proteins was also demonstrated; when added to lymphocytes cultures, AaG, aAT and CER exert an inhibiting effect on lymphocyte proliferation at concentrations which are lower than those necessary to obtain the same effect when only one protein is added [14].…”

Expression of haptoglobin-related protein and its potential role as a tumor antigen.

“…A synthetic peptide corresponding to the 34 N-terminal residues of the predicted HPR gene product (4) was synthesized by the Protein Chemistry Facility on an Applied Biosystems model 43A peptide synthesizer (15). Because histidine coupling is inefficient, lysine was conservatively substituted for the histidine in position 28. For immunization, the peptide was conjugated to keyhole limpet hemocyanin (KLH) (Boehringer Mannheim) essentially as described (16).…”