New research uncovers how tumor acidity suppresses immune response
A recent study published in The EMBO Journal uncovers how the acidic environment of solid tumors hampers the function of CD8+ T cells. These findings shed light on how acidity disrupts critical immune cell signaling pathways and points to potential new therapeutic strategies for enhancing cancer immunotherapy.
This new research*, led by Dr Romain Vuillefroy de Silly and directed by Dr Melita Irving, part of the Lausanne Branch of the Ludwig Institute for Cancer Research, discovered how the acidic nature of solid tumors undermines the effectiveness of CD8+ T cells, a crucial component of the immune system’s fight against cancer. The study shows that low pH impairs the cells' ability to expand and mount a robust immune response by interfering with key signaling pathways such as IL-2, mTORC1, and c-Myc as well as amino acid metabolism.
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The study’s findings suggest that therapeutic strategies aimed at normalizing tumor pH, combined with existing immunotherapies like immune checkpoint inhibitors and adoptive T-cell transfer, could significantly improve patient outcomes.
"Our research highlights the profound effects of acidity on T-cell function, revealing it as a critical barrier to effective cancer treatment," said Dr Irving. "Addressing this challenge may unlock new approaches to enhance the efficacy of immunotherapies in solid tumors."
These findings offer valuable insights into how tumors evade immune surveillance and highlight the potential of therapeutic strategies that target the tumor’s acidic environment. By combining pH regulation with immunotherapies like immune checkpoint blockade, we may be able to boost the effectiveness of cancer treatments and improve patient outcomes.
Research for this study was supported in part by the Swiss National Science Foundation, the Ludwig Institute for Cancer Research and the University of Lausanne.
* Acidity suppresses CD8 + T-cell function by perturbing IL-2, mTORC1, andc-Myc signaling
by Carine Dournes Söhnlein (DO communication)