What is it about?
Tumours do not develop in isolation. Their surrounding microenvironment is shaped by tumour metabolism, creating conditions that can promote tumour survival while suppressing anti-tumour immunity. This review examines the role of extracellular acidosis in the tumour microenvironment, focusing on how low pH affects tumour cells, stromal cells and immune cells. We explore how acidity contributes to immune escape by inhibiting the activity of immune effector cells while promoting immunosuppressive phenotypes, and consider approaches for targeting tumour acidity therapeutically.
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Photo by National Cancer Institute on Unsplash
Why is it important?
The tumour microenvironment can be an important barrier to effective cancer treatment. Acidity affects multiple components of the immune response, including T cells, NK cells, dendritic cells, macrophages and neutrophils, while also promoting tumour-cell adaptations associated with survival, invasion and metastasis. These effects may help explain why targeting tumour cells alone is not always sufficient. Understanding how the acidic microenvironment contributes to immune escape may therefore identify opportunities to improve existing cancer therapies by modifying the conditions in which tumours and immune cells interact.
Perspectives
The acidic tumour microenvironment represents a potentially important therapeutic target, but translating this concept into clinical practice remains challenging. Tumours use multiple, partly redundant mechanisms to regulate intracellular and extracellular pH, making it unlikely that a single target will be sufficient. Emerging approaches, including inhibition of proton-extrusion mechanisms and pH-responsive drug delivery systems, may offer ways of altering the tumour microenvironment while limiting systemic effects. Combining these approaches with existing cancer therapies could potentially improve anti-tumour immune responses and treatment efficacy.
Dr Catherine Worsley
University of Pretoria
Read the Original
This page is a summary of: The acidic tumour microenvironment: Manipulating the immune response to elicit escape, Human Immunology, May 2022, Elsevier,
DOI: 10.1016/j.humimm.2022.01.014.
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