Interference With Immune Response at the Level of Generating Effector Cells by Tumor-Associated Haptoglobin

Abstract

Most of the immune response regulators identified to date proved to be products of tumor, of an immune system or of combinations of such systems or to be tumor-induced host products. We have described how the haptoglobin isolated from cancer patients can impose serious hindrance to cell-mediated immune functions in vivo and in vitro under the pathophysiologic concentrations seen in these patients. Because the tumor-associated haptoglobin interferes with the innate and adaptive immune functions, elimination of the haptoglobin by passive removal or by active therapy could be an important adjunct for immunotherapy in cancer patients.

Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

“…In a variety ofmalignancies, haptoglobin concentration correlates with disease progression (40)(41)(42)(43). Angiogenesis is an important phenomenon in all of these conditions (44)(45)(46).…”

“…Immunochemically and functionally different haptoglobins have been described in other pathological conditions. For example, haptoglobin purified from malignant effusions is structurally similar to fetal haptoglobin and has immunosuppressive properties that are more potent than that of adult haptoglobin (42)(43)(44). Cancer or fetal haptoglobins and normal adult haptoglobin differ primarily because of postranslational modifications that include variations in glycosylation (42,43).…”

“…For example, haptoglobin purified from malignant effusions is structurally similar to fetal haptoglobin and has immunosuppressive properties that are more potent than that of adult haptoglobin (42)(43)(44). Cancer or fetal haptoglobins and normal adult haptoglobin differ primarily because of postranslational modifications that include variations in glycosylation (42,43). Abnormally glycosylated forms of haptoglobin have also been described in chronic inflammatory diseases such as rheumatoid arthritis 982 Cid, Grant, Hoffman, Auerbach, Fauci, and Kleinman (49).…”

Haptoglobin and the Th1/Th2 balance: hints fromin vitroandin vivostudies

“…1 Hp inhibits the respiratory burst and the rise in intracellular calcium in neutrophils following fMLP stimulation. 2 It also suppresses lectin-and lipopolysaccharide (LPS)-induced proliferation of T lymphocytes and B-cell mitogenesis, 1,[3][4][5][6] and modulates macrophage function. 3 However, the mechanism of action of Hp on the immune system remains enigmatic.…”

Induction of Haptoglobin by All-trans Retinoic Acid in THP-1 Human Monocytic Cell Line

“…Some researchers have reported Hp-related proteins that have immunosuppressive activities (17)(18)(19). To shown).…”