Increasing Tumor Extracellular pH by an Oral Alkalinizing Agent Improves Antitumor Responses of Anti-PD-1 Antibody: Implication of Relationships between Serum Bicarbonate Concentrations, Urinary pH, and Therapeutic Outcomes

نویسندگان

چکیده

Acidic extracellular pH (pHe) is characteristic of the tumor microenvironment. Several reports suggest that increasing pHe improves response immune checkpoint inhibitors in murine models. To increase pHe, either sodium bicarbonate (NaHCO3) or citric acid/potassium-sodium citrate (KNa-cit) was chronically administered to mice. It hypothesized ions (HCO3−), produced from these alkalinizing agents vivo, increased tumor, and excess HCO3− eliminated into urine urinary values. However, there little published information on effect changing serum concentrations, concentrations values therapeutic outcomes immunotherapy. In this study, we report oral administration NaHCO3 KNa-cit responses anti-programmed cell death-1 (PD-1) antibody, an inhibitor, a B16 melanoma model. addition, daily agent blood corresponding pHe. Serum also correlated with There clear relationship between antitumor effects immunotherapy anti-PD-1 antibody. Our results imply values, may be important factors predict clinical immunotherapeutic agent, when combined such as KNa-cit.

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ژورنال

عنوان ژورنال: Biological & Pharmaceutical Bulletin

سال: 2021

ISSN: ['1347-5215', '0918-6158']

DOI: https://doi.org/10.1248/bpb.b21-00076