Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells.

DANTAS EZEQUIEL; MERLOTTI ANTONELA; SABATTE JUAN; ERRA DIAZ FERNANDO; VARESE AUGUSTO; GEFFNER JORGE; ERRA DIAZ FERNANDO; VARESE AUGUSTO; GEFFNER JORGE; PEREYRA GERBER PEHUÉN; OSTROWSKI MATIAS; PEREYRA GERBER PEHUÉN; OSTROWSKI MATIAS; DANTAS EZEQUIEL; MERLOTTI ANTONELA; SABATTE JUAN

Oncotarget

Impact Journals

Lugar: Orchard Park; Año: 2016 vol. 7 p. 74203 - 74216

1949-2553

Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer diseases. However, few studies have addressed the effect of extracellular pH on the immune response. Here, we analyzed whether low pH could modulate complement-dependent cytotoxicity (CDC) against IgG-coated cells. Using human serum as a complement source, we found that extracellular pH values of 5.5 and 6.0 strongly inhibit CDC against either B lymphoblast cell lines coated with the chimeric anti-CD20 mAb rituximab or PBMCs coated with the humanized anti-CD52 mAb alemtuzumab. Suppression of CDC by low pH was observed either in cells suspended in culture medium or in whole blood assays. Interestingly, not only CDC against IgG-coated cells, but also the activation of the complement system induced by the alternative and lectin pathways was prevented by low pH. Tumor-targeting mAbs represent one of the most successful tools for cancer therapy, however, the use of mAb monotherapy has only modest effects on solid tumors. Our present results suggest that severe acidosis, a hallmark of solid tumors, might impair complement-mediated tumor