Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy

Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that…

• HL
  H. Lee Moffitt Cancer Center and Research Institute

  Award: P30CA076292
• UP
  U.S. Public Health Service

  Awards: P50CA168536, R01CA077575