Acidity suppresses CD8 + T-cell function by perturbing IL-2, mTORC1, and c-Myc signaling

Area of Science:

• Immunology
• Cancer Biology
• Cellular Physiology

Background:

• CD8+ T cells are crucial for tumor control.
• The tumor microenvironment, including low pH (acidity), can suppress T cell function.

Purpose of the Study:

• To investigate the impact of acidity on CD8+ T cell function.
• To elucidate the molecular mechanisms underlying acidity-induced T cell suppression.

Main Methods:

• Assessing T cell expansion, cytokine secretion, and cytolytic capacity under acidic conditions.
• Analyzing mTORC1 signaling, c-Myc levels, and intracellular metabolites.
• Investigating the role of intracellular pH in T cell function.

Main Results:

• Acidity impairs T cell expansion by reducing IL-2 responsiveness.
• Low pH decreases cytokine secretion and the cytolytic capacity of CD8+ T cells.
• Acidity suppresses mTORC1 signaling and c-Myc levels through various mechanisms, impacting T cell function.

Conclusions:

• Acidity broadly suppresses CD8+ T cell functions, including proliferation, cytokine production, and cytotoxicity.
• Mechanisms involve impaired IL-2 signaling, reduced mTORC1 activity, and decreased c-Myc levels.
• Effective control of intracellular pH is essential for restoring T cell function in the tumor microenvironment.