Oncotarget

Research Papers:

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

Ezequiel Dantas, Fernando Erra Díaz, Pehuén Pereyra Gerber, Antonela Merlotti, Augusto Varese, Matías Ostrowski, Juan Sabatté and Jorge Geffner _

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Oncotarget. 2016; 7:74203-74216. https://doi.org/10.18632/oncotarget.12412

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Abstract

Ezequiel Dantas1, Fernando Erra Díaz1, Pehuén Pereyra Gerber1, Antonela Merlotti1, Augusto Varese1, Matías Ostrowski1, Juan Sabatté1, Jorge Geffner1

1Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Argentina

Correspondence to:

Jorge Geffner, email: [email protected]

Keywords: complement, pH, acidosis, cancer, rituximab

Received: March 19, 2016    Accepted: September 20, 2016    Published: October 3, 2016

ABSTRACT

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 destruction directed by mAb.


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