Metabolic modulation of pH flux in T cells in the tumor microenvironment
Date
2025
Authors
Titosky, Kesia
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
T cell immunotherapy is an effective treatment for malignant cancers of the blood but has had limited success in solid tumors (1,2). Solid tumors are the leading cause of cancer-related deaths in Canada, and a projected 1,950 Canadians are predicted to die from ovarian cancer by the end of 2023 (3). The solid tumor microenvironment proves a challenging arena: hostile, with low oxygen, varied nutrient levels, poor blood flow, and a buildup of acidic hydrogen ions (acidosis), which creates an inhospitable environment (4,5). Carbonic anhydrase IX (CAIX), a tumor-associated membrane enzyme, is a critical molecule for regulating the internal pH (pHi) of tumor cells (6). Without tumor enhancements such as CAIX, tumor-fighting T cells have insufficient means to control pHi, often losing in the constant battle with metabolic acidosis (7). Using genetic engineering, our lab has successfully transduced T cells with CAIX, but we found that it did not have any substantial effects in improving T cell function in acidic environments.