Acid Inhibition of Immunity

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Project Summary:

The tumor microenvironment is heterogeneous and dynamic in its composition and evolution. Solid tumors consist of multiple cell types including cancer, stromal, and immune cells and a large variety of extracellular matrix proteins and chemical signals. The interactions between stromal-, immune-, cancer cells, and the extracellular matrix, arrange tumor growth and development. Due to insufficient blood perfusion, hypoxia, inflammation, and glucose metabolism, the tumor microenvironment is acidic. The clinical evidence about the effect of metabolic alterations shows that metabolic acidosis is often associated with immunodeficiency, and suggests that T cells could be extremely sensitive to pH variations.

Therapeutic resistance is a crucial factor in cancer prognosis. The acidic pH and hypoxic microenvironment of solid tumors have a considerable influence to the efficacy of chemo-, radio-, and immuno-therapies. Combined approaches may lead to improved clinical trial design and ultimately identify effective regimens to overcome treatment resistance.

The role of neutralizing tumor acidosis in improving treatment response is not known with certainty, but recent data demonstrated that acidification makes stroma or endothelium to product inflammatory cytokines. While acidification may send an inflammatory signal, T cells are not able to activate until pH increment occurs. In tumors, raising tumor pH through buffer therapy may permit improving the response by promoting T cell activation.

In the scope of this work the effect of neutralization of tumor acidity will be combined with immunotherapy to boost immunotherapy responses.

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Project Members

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Sultan Damgaci, MS

Research Associate

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Christian Pilot

Research Associate